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Sodium sensitivity of blood pressure in Chinese populations

Abstract

Hypertension is an enormous public-health challenge in the world due to its high prevalence and consequent increased cardiovascular disease morbidity and mortality. Observational epidemiologic studies and clinical trials have demonstrated a causal relationship between sodium intake and elevated blood pressure (BP). However, BP changes in response to sodium intervention vary among individuals—a trait called sodium sensitivity. This paper aims to review the recent advances in sodium-sensitivity research in Chinese and other populations. Older age, female gender, and black race are associated with high sodium sensitivity. Both genetic and environmental factors influence BP sodium sensitivity. Physical activity and dietary potassium intake are associated with reduced sodium sensitivity while obesity, metabolic syndrome, and elevated BP are associated with increased sodium sensitivity. Familial studies have documented a moderate heritability of sodium sensitivity. Candidate gene association studies, genome-wide association studies, whole-exome, and whole-genome sequencing studies have been conducted to elucidate the genomic mechanisms of sodium sensitivity. The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) study, the largest family-based feeding study to date, was conducted among 1906 Han Chinese in rural northern China. This study showed that ~32.4% of Chinese adults were sodium sensitive. Additionally, several genetic variants were found to be associated with sodium sensitivity. Findings from the GenSalt Study and others indicate that sodium sensitivity is a reproducible trait and both lifestyle factors and genetic variants play a role in this complex trait. Discovering biomarkers and underlying mechanisms for sodium sensitivity will help to develop individualized intervention strategies for hypertension.

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References

  1. Mills KT, Bundy JD, Kelly TN, Reed J, Kearney PM, Reynolds K, et al. Global disparities of hypertension prevalence and control: a systematic analysis of population-based studies from 90 countries. Circulation. 2016;134:441–50.

    Article  PubMed  PubMed Central  Google Scholar 

  2. He J, Gu D, Chen J, Wu X, Kelly TN, Huang JF, et al. Premature deaths attributable to blood pressure in China: a prospective cohort study. Lancet. 2009;374:1765–72.

    Article  PubMed  Google Scholar 

  3. Lawes CM, Vander Hoorn S, Rodgers A. Global burden of blood-pressure-related disease, 2001. Lancet. 2008;371:1513–8.

    Article  PubMed  Google Scholar 

  4. He J, Tell GS, Tang YC, Mo PS, He GQ. Relation of electrolytes to blood pressure in men. The Yi people study. Hypertension. 1991;17:378–85.

    Article  CAS  PubMed  Google Scholar 

  5. Elliott P, Stamler J, Nichols R, Dyer AR, Stamler R, Kesteloot H, et al. Intersalt revisited: further analyses of 24h sodium excretion and blood pressure within and across populations. BMJ. 1996;312:1249–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. He FJ, Li J, MacGregor GA. Effect of longer term modest salt reduction on blood pressure: Cochrane systematic review and meta-analysis of randomised trials. BMJ. 2013;346:f1325 https://doi.org/10.1136/bmj.f1325

    Article  PubMed  Google Scholar 

  7. Newberry SJ, Chung M, Anderson CA, Chen C, Fu Z, Tang A, et al. Sodium and potassium intake: effects on chronic disease outcomes and risks. Comparative effectiveness review no. 206. (Prepared by the RAND Southern California Evidence-based Practice Center under Contract No. 290-2015-00010-I.) AHRQ Publication No. 18-EHC009-EF. Rockville, MD: Agency for Healthcare Research and Quality; 2018.

  8. Kawasaki T, Delea CS, Bartter FC, Smith H. The effect of high-sodium and low-sodium intakes on blood pressure and other related variables in human subjects with idiopathic hypertension. Am J Med. 1978;64:193–8.

    Article  CAS  PubMed  Google Scholar 

  9. Weinberger MH. Salt sensitivity of blood pressure in humans. Hypertension. 1996;27:481–90.

    Article  CAS  PubMed  Google Scholar 

  10. Frame AA, Wainford RD. Renal sodium handling and sodium sensitivity. Kidney Res Clin Pract. 2017;36:117–31.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Weinberger MH, Fineberg NS, Fineberg SE, Weinberger M. Salt sensitivity, pulse pressure, and death in normal and hypertensive humans. Hypertension. 2001;37:429–32.

    Article  CAS  PubMed  Google Scholar 

  12. Morimoto A, Uzu T, Fujii T, Nishimura M, Kuroda S, Nakamura S, et al. Sodium sensitivity and cardiovascular events in patients with essential hypertension. Lancet. 1997;350:1734–7.

    Article  CAS  PubMed  Google Scholar 

  13. He J, Gu D, Chen J, Jaquish CE, Rao DC, Hixson JE, et al. Gender difference in blood pressure responses to dietary sodium intervention in the GenSalt study. J Hypertens. 2009;27:48–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sharma AM, Schattenfroh S, Kribben A, Distler A. Reliability of salt-sensitivity testing in normotensive subjects. Klin Wochenschr. 1989;67:632–4.

    Article  CAS  PubMed  Google Scholar 

  15. Gu D, Zhao Q, Chen J, Chen JC, Huang J, Bazzano LA, et al. Reproducibility of blood pressure responses to dietary sodium and potassium interventions. The GenSalt study. Hypertension. 2013;62:499–505.

    Article  CAS  PubMed  Google Scholar 

  16. Fujita T. The effect of high-sodium intake and furosemide on blood pressure and other related variables in salt-sensitive hypertension. Jpn J Med. 1982;21:157–8.

    Article  CAS  PubMed  Google Scholar 

  17. Koolen MI, Bussemaker-Verduyn den Boer E, van Brummelen P. Clinical biochemical and haemodynamic correlates of sodium sensitivity in essential hypertension. J Hypertens Suppl. 1983;1:21–23.

    CAS  PubMed  Google Scholar 

  18. Takeshita A, Imaizumi T, Ashihara T, Nakamura M. Characteristics of responses to salt loading and deprivation in hypertensive subjects. Circ Res. 1982;51:457–64.

    Article  CAS  PubMed  Google Scholar 

  19. Campese VM, Romoff MS, Levitan D, Saglikes Y, Friedler RM, Massry SG. Abnormal relationship between sodium-intake and sympathetic nervous-system activity in salt-sensitive patients with essential-hypertension. Kidney Int. 1982;21:371–8.

    Article  CAS  PubMed  Google Scholar 

  20. Wright JT Jr., Rahman M, Scarpa A, Fatholahi M, Griffin V, Jean-Baptiste R, et al. Determinants of salt sensitivity in black and white normotensive and hypertensive women. Hypertension. 2003;42:1087–92.

    Article  CAS  PubMed  Google Scholar 

  21. Morris RC Jr, Sebastian A, Forman A, Tanaka M, Schmidlin O. Normotensive salt sensitivity: effects of race and dietary potassium. Hypertension. 1999;33:18–23.

    Article  CAS  PubMed  Google Scholar 

  22. Weinberger MH, Fineberg NS. Sodium and volume sensitivity of blood pressure. Age and pressure change over time. Hypertension. 1991;18:67–71.

    Article  CAS  PubMed  Google Scholar 

  23. Frame AA, Wainford RD. Mechanisms of altered renal sodium handling in age-related hypertension. Am J Physiol Ren Physiol. 2018;315:F1–F6.

    Article  CAS  Google Scholar 

  24. Miller JZ, Weinberger MH, Daugherty SA, Fineberg NS, Christian JC, Grim CE. Heterogeneity of blood pressure response to dietary sodium restriction in normotensive adults. J Chronic Dis. 1987;40:245–50.

    Article  CAS  PubMed  Google Scholar 

  25. Hurwitz S, Fisher ND, Ferri C, Hopkins PN, Williams GH, Hollenberg NK. Controlled analysis of blood pressure sensitivity to sodium intake: interactions with hypertension type. J Hypertens. 2003;21:951–9.

    Article  CAS  PubMed  Google Scholar 

  26. Wilson DK, Bayer L, Sica DA. Variability in salt sensitivity classifications in black male versus female adolescents. Hypertension. 1996;28:250–5.

    Article  CAS  PubMed  Google Scholar 

  27. Vollmer WM, Sacks FM, Ard J, Appel LJ, Bray GA, Simons-Morton DG, et al. Effects of diet and sodium intake on blood pressure: subgroup analysis of the DASH-sodium trial. Ann Intern Med. 2001;135:1019–28.

    Article  CAS  PubMed  Google Scholar 

  28. Stachenfeld NS, Taylor HS. Effects of estrogen and progesterone administration on extracellular fluid. J Appl Physiol. 2004;96:1011–8.

    Article  CAS  PubMed  Google Scholar 

  29. Stachenfeld NS, DiPietro L, Palter SF, Nadel ER. Estrogen influences osmotic secretion of AVP and body water balance in postmenopausal women. Am J Physiol. 1998;274:R187–R195.

    CAS  PubMed  Google Scholar 

  30. Kelly TN, Rebholz CM, Gu D, Hixson JE, Rice TK, Cao J, et al. Analysis of sex hormone genes reveals gender differences in the genetic etiology of blood pressure salt sensitivity: the GenSalt study. Am J Hypertens. 2013;26:191–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med. 2001;344:3–10.

    Article  CAS  PubMed  Google Scholar 

  32. Luft FC, Rankin LI, Bloch R, Weyman AE, Willis LR, Murray RH, et al. Cardiovascular and humoral responses to extremes of sodium intake in normal black and white men. Circulation. 1979;60:697–706.

    Article  CAS  PubMed  Google Scholar 

  33. Godden JO, Roth GM, Hines EA, Schlegel JF. The changes in the intra-arterial pressure during immersion of the hand in ice-cold water. Circulation. 1955;12:963–73.

    Article  CAS  PubMed  Google Scholar 

  34. Victor RG, Leimbach WN Jr, Seals DR, Wallin BG, Mark AL. Effects of the cold pressor test on muscle sympathetic nerve activity in humans. Hypertension. 1987;9:429–36.

    Article  CAS  PubMed  Google Scholar 

  35. Kasagi F, Akahoshi M, Shimaoka K. Relation between cold pressor test and development of hypertension based on 28-year follow-up. Hypertension. 1995;25:71–76.

    Article  CAS  PubMed  Google Scholar 

  36. Strazzullo P, Strazzullo P, Barbato A, Vuotto P, Galletti F. Relationships between salt sensitivity of blood pressure and sympathetic nervous system activity: a short review of evidence. Clin Exp Hypertens. 2001;23:25–33.

    Article  CAS  PubMed  Google Scholar 

  37. Chen J, Gu D, Jaquish CE, Chen CS, Rao DC, Liu D, et al. Association between blood pressure responses to the cold pressor test and dietary sodium intervention in a Chinese population. Arch Intern Med. 2008;168:1740–6.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Zhao Q, Gu D, Chen J, Li J, Cao J, Lu F, et al. Blood pressure responses to dietary sodium and potassium interventions and the cold pressor test: the GenSalt replication study in rural North China. Am J Hypertens. 2014;27:72–80.

    Article  CAS  PubMed  Google Scholar 

  39. Zhao Q, Bazzano LA, Cao J, Li J, Chen J, Huang J. et al. Reproducibility of blood pressure response to the cold pressor test: the GenSalt Study. Am J Epidemiol. 2012;176(Suppl. 7):S91–98.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Rocchini AP, Key J, Bondie D, Chico R, Moorehead C, Katch V, et al. The effect of weight loss on the sensitivity of blood pressure to sodium in obese adolescents. N Engl J Med. 1989;321:580–5.

    Article  CAS  PubMed  Google Scholar 

  41. Uzu T, Kimura G, Yamauchi A, Kanasaki M, Isshiki K, Araki SI, et al. Enhanced sodium sensitivity and disturbed circadian rhythm of blood pressure in essential hypertension. J Hypertens. 2006;24:1627–32.

    Article  CAS  PubMed  Google Scholar 

  42. Chen J, Gu D, Huang J, Rao DC, Jaquish CE, Hixson JE, et al. Metabolic syndrome and salt sensitivity of blood pressure in non-diabetic people in China: a dietary intervention study. Lancet. 2009;373:829–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Strazzullo P, Barba G, Cappuccio FP, Siani A, Trevisan M, Farinaro E, et al. Altered renal sodium handling in men with abdominal adiposity: a link to hypertension. J Hypertens. 2001;19:2157–64.

    Article  CAS  PubMed  Google Scholar 

  44. Hoffmann IS, Cubeddu LX. Increased blood pressure reactivity to dietary salt in patients with the metabolic syndrome. J Hum Hypertens. 2007;21:438–44.

    Article  CAS  PubMed  Google Scholar 

  45. Shimamoto K, Hirata A, Fukuoka M, Higashiura K, Miyazaki Y, Shiiki M, et al. Insulin sensitivity and the effects of insulin on renal sodium handling and pressor systems in essential hypertensive patients. Hypertension. 1994;23(1 Suppl):I29–33.

    Article  CAS  PubMed  Google Scholar 

  46. Nizar JM, Bhalla V. Molecular mechanisms of sodium-sensitive hypertension in the metabolic syndrome. Curr Hypertens Rep. 2017;19:60.

    Article  CAS  PubMed  Google Scholar 

  47. Carnethon MR, Evans NS, Church TS, Lewis CE, Schreiner PJ, Jacobs DR Jr, et al. Joint associations of physical activity and aerobic fitness on the development of incident hypertension: coronary artery risk development in young adults. Hypertension. 2010;56:49–55.

    Article  CAS  PubMed  Google Scholar 

  48. Whelton SP, Chin A, Xin X, He J. Effect of aerobic exercise on blood pressure: a meta-analysis of randomized, controlled trials. Ann Intern Med. 2002;136:493–503.

    Article  PubMed  Google Scholar 

  49. Rebholz CM, Gu D, Chen J, Huang JF, Cao J, Chen JC, et al. Physical activity reduces salt sensitivity of blood pressure: the Genetic Epidemiology Network of Salt Sensitivity Study. Am J Epidemiol. 2012;176(Suppl. 7):S106–113.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Whelton PK, He J, Cutler JA, Brancati FL, Appel LJ, Follmann D, et al. Effects of oral potassium on blood pressure. Meta-analysis of randomized controlled clinical trials. JAMA. 1997;277:1624–32.

    Article  CAS  PubMed  Google Scholar 

  51. Coruzzi P, Brambilla L, Brambilla V, Gualerzi M, Rossi M, Parati G, et al. Potassium depletion and salt sensitivity in essential hypertension. J Clin Endocrinol Metab. 2001;86:2857–62.

    Article  CAS  PubMed  Google Scholar 

  52. Ray PE, Suga S, Liu XH, Huang X, Johnson RJ. Chronic potassium depletion induces renal injury, salt sensitivity, and hypertension in young rats. Kidney Int. 2001;59:1850–8.

    Article  CAS  PubMed  Google Scholar 

  53. Rotimi CN, Cooper RS, Cao G, Ogunbiyi O, Ladipo M, Owoaje E, et al. Maximum-likelihood generalized heritability estimate for blood pressure in Nigerian families. Hypertension. 1999;33:874–8.

    Article  CAS  PubMed  Google Scholar 

  54. Mitchell GF, DeStefano AL, Larson MG, Benjamin EJ, Chen MH, Vasan RS, et al. Heritability and a genome-wide linkage scan for arterial stiffness, wave reflection, and mean arterial pressure: the Framingham Heart Study. Circulation. 2005;112:194–9.

    Article  PubMed  Google Scholar 

  55. Miller JZ, Weinberger MH, Christian JC, Daugherty SA. Familial resemblance in the blood pressure response to sodium restriction. Am J Epidemiol. 1987;126:822–30.

    Article  CAS  PubMed  Google Scholar 

  56. Svetkey LP, McKeown SP, Wilson AF. Heritability of salt sensitivity in black Americans. Hypertension. 1996;28:854–8.

    Article  CAS  PubMed  Google Scholar 

  57. Gu D, Rice T, Wang S, Yang W, Gu C, Chen CS, et al. Heritability of blood pressure responses to dietary sodium and potassium intake in a Chinese population. Hypertension. 2007;50:116–22.

    Article  CAS  PubMed  Google Scholar 

  58. Dengel DR, Brown MD, Ferrell RE, Supiano MA. Role of angiotensin converting enzyme genotype in sodium sensitivity in older hypertensives. Am J Hypertens. 2001;14:1178–84.

    Article  CAS  PubMed  Google Scholar 

  59. Poch E, Gonzalez D, Giner V, Bragulat E, Coca A, de La, Sierra A. Molecular basis of salt sensitivity in human hypertension: evaluation of renin-angiotensin-aldosterone system gene polymorphisms. Hypertension. 2001;38:1204–9.

    Article  CAS  PubMed  Google Scholar 

  60. Hiraga H, Oshima T, Watanabe M, Ishida M, Ishida T, Shingu T, et al. Angiotensin I-converting enzyme gene polymorphism and salt sensitivity in essential hypertension. Hypertension. 1996;27:569–72.

    Article  CAS  PubMed  Google Scholar 

  61. Johnson AG, Nguyen TV, Davis D. Blood pressure is linked to salt intake and modulated by the angiotensinogen gene in normotensive and hypertensive elderly subjects. J Hypertens. 2001;19:1053–60.

    Article  CAS  PubMed  Google Scholar 

  62. Schorr U, Blaschke K, Beige J, Distler A, Sharma AM. Angiotensinogen M235T variant and salt sensitivity in young normotensive Caucasians. J Hypertens. 1999;17:475–9.

    Article  CAS  PubMed  Google Scholar 

  63. Svetkey LP, Harris EL, Martin E, Vollmer WM, Meltesen GT, Ricchiuti V, et al. Modulation of the BP response to diet by genes in the renin-angiotensin system and the adrenergic nervous system. Am J Hypertens. 2011;24:209–17.

    Article  CAS  PubMed  Google Scholar 

  64. Hunt SC, Cook NR, Oberman A, Cutler JA, Hennekens CH, Allender PS, et al. Angiotensinogen genotype, sodium reduction, weight loss, and prevention of hypertension: trials of hypertension prevention, phase II. Hypertension. 1998;32:393–401.

    Article  CAS  PubMed  Google Scholar 

  65. Hunt SC, Geleijnse JM, Wu LL, Witteman JC, Williams RR, Grobbee DE. Enhanced blood pressure response to mild sodium reduction in subjects with the 235T variant of the angiotensinogen gene. Am J Hypertens. 1999;12:460–6.

    Article  CAS  PubMed  Google Scholar 

  66. Norat T, Bowman R, Luben R, Welch A, Khaw KT, Wareham N, et al. Blood pressure and interactions between the angiotensin polymorphism AGT M235T and sodium intake: a cross-sectional population study. Am J Clin Nutr. 2008;88:392–7.

    Article  CAS  PubMed  Google Scholar 

  67. Iwai N, Kajimoto K, Tomoike H, Takashima N. Polymorphism of CYP11B2 determines salt sensitivity in Japanese. Hypertension. 2007;49:825–31.

    Article  CAS  PubMed  Google Scholar 

  68. Wrona A, Widecka K, Adler G, Czekalski S, Ciechanowicz A. Promoter variants of aldosterone synthase gene (CYP11B2) and salt-sensitivity of blood pressure. Pol Arch Med Wewn. 2004;111:191–7.

    CAS  PubMed  Google Scholar 

  69. Pamies-Andreu E, Ramirez-Lorca R, García-Junco PS, Muniz-Grijalbo O, Vallejo-Maroto I, Morillo SG, et al. Renin-angiotensin-aldosterone system and G-protein beta-3 subunit gene polymorphisms in salt-sensitive essential hypertension. J Hum Hypertens. 2003;17:187–91.

    Article  CAS  PubMed  Google Scholar 

  70. Miyaki K, Hara A, Araki J, Zhang L, Song Y, Kimura T, et al. C3123A polymorphism of the angiotensin II type 2 receptor gene and salt sensitivity in healthy Japanese men. J Hum Hypertens. 2006;20:467–9.

    Article  CAS  PubMed  Google Scholar 

  71. Cicila GT, Garrett MR, Lee SJ, Liu J, Dene H, Rapp JP. High-resolution mapping of the blood pressure QTL on chromosome 7 using Dahl rat congenic strains. Genomics. 2001;72:51–60.

    Article  CAS  PubMed  Google Scholar 

  72. Lovati E, Ferrari P, Dick B, Jostarndt K, Frey BM, Frey FJ, et al. Molecular basis of human salt sensitivity: the role of the 11beta-hydroxysteroid dehydrogenase type 2. J Clin Endocrinol Metab. 1999;84:3745–9.

    CAS  PubMed  Google Scholar 

  73. Agarwal AK, Giacchetti G, Lavery G, Nikkila H, Palermo M, Ricketts M, et al. CA-repeat polymorphism in intron 1 of HSD11B2: effects on gene expression and salt sensitivity. Hypertension. 2000;36:187–94.

    Article  CAS  PubMed  Google Scholar 

  74. Alikhani-Koupaei R, Fouladkou F, Fustier P, Cenni B, Sharma AM, Deter H-C, et al. Identification of polymorphisms in the human 11beta-hydroxysteroid dehydrogenase type 2 gene promoter: functional characterization and relevance for salt sensitivity. FASEB J. 2007;21:3618–28.

    Article  CAS  PubMed  Google Scholar 

  75. Zhao Q, Hixson JE, Rao DC, Gu D, Jaquish CE, Rice T, et al. Genetic variants in the apelin system and blood pressure responses to dietary sodium interventions: a family-based association study. J Hypertens. 2010;28:756–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Gu D, Kelly TN, Hixson JE, Chen J, Liu D, Chen JC, et al. Genetic variants in the renin-angiotensin-aldosterone system and salt sensitivity of blood pressure. J Hypertens. 2010;28:1210–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Rossier BC, Pradervand S, Schild L, Hummler E. Epithelial sodium channel and the control of sodium balance: interaction between genetic and environmental factors. Annu Rev Physiol. 2002;64:877–97.

    Article  CAS  PubMed  Google Scholar 

  78. Freitas SR. Molecular genetics of salt-sensitivity and hypertension: role of renal epithelial sodium channel genes. Am J Hypertens. 2017;31:172–4.

    Article  CAS  Google Scholar 

  79. Adamzik M, Frey UH, Bitzer K, Jakob H, Baba HA, Schmieder RE, et al. A novel-1364A/C aquaporin 5 gene promoter polymorphism influences the responses to salt loading of the renin-angiotensin-aldosterone system and of blood pressure in young healthy men. Basic Res Cardiol. 2008;103:598–610.

    Article  CAS  PubMed  Google Scholar 

  80. Barlassina C, Dal Fiume C, Lanzani C, Manunta P, Guffanti G, Ruello A, et al. Common genetic variants and haplotypes in renal CLCNKA gene are associated to salt-sensitive hypertension. Hum Mol Genet. 2007;16:1630–8.

    Article  CAS  PubMed  Google Scholar 

  81. Citterio L, Simonini M, Zagato L, Salvi E, Carpini SD, Lanzani C, et al. Genes involved in vasoconstriction and vasodilation system affect salt-sensitive hypertension. PLoS One. 2011;6:e19620.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Manunta P, Lavery G, Lanzani C, Braund PS, Simonini M, Bodycote C, et al. Physiological interaction between alpha-adducin and WNK1-NEDD4L pathways on sodium-related blood pressure regulation. Hypertension. 2008;52:366–72.

    Article  CAS  PubMed  Google Scholar 

  83. Osada Y, Miyauchi R, Goda T, Kasezawa N, Horiike H, Iida M, et al. Variations in the WNK1 gene modulates the effect of dietary intake of sodium and potassium on blood pressure determination. J Hum Genet. 2009;54:474–8.

    Article  CAS  PubMed  Google Scholar 

  84. Hoffmann IS, Tavares-Mordwinkin R, Castejon AM, Alfieri AB, Cubeddu LX. Endothelial nitric oxide synthase polymorphism, nitric oxide production, salt sensitivity and cardiovascular risk factors in Hispanics. J Hum Hypertens. 2005;19:233–40.

    Article  CAS  PubMed  Google Scholar 

  85. Carey RM, Schoeffel CD, Gildea JJ, Jones JE, McGrath HE, Gordon LN, et al. Salt sensitivity of blood pressure is associated with polymorphisms in the sodium-bicarbonate cotransporter. Hypertension. 2012;60:1359–66.

    Article  CAS  PubMed  Google Scholar 

  86. Rao AD, Sun B, Saxena A, Hopkins PN, Jeunemaitre X, Brown NJ, et al. Polymorphisms in the serum- and glucocorticoid-inducible kinase 1 gene are associated with blood pressure and renin response to dietary salt intake. J Hum Hypertens. 2013;27:176–80.

    Article  CAS  PubMed  Google Scholar 

  87. Zhao Q, Gu D, Hixson JE, Liu DP, Rao DC, Jaquish CE, et al. Common variants in epithelial sodium channel genes contribute to salt sensitivity of blood pressure: the GenSalt study. Circ Cardiovasc Genet. 2011;4:375–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Li C, Yang X, He J, Hixson JE, Gu D, Rao DC, et al. A gene-based analysis of variants in the serum/glucocorticoid regulated kinase (SGK) genes with blood pressure responses to sodium intake: The GenSalt Study. PLoS One. 2014;9:e98432.

  89. Guo L, Liu F, Chen S, Yang X, Huang J, He J, et al. Common variants in the Na(+)-coupled bicarbonate transporter genes and salt sensitivity of blood pressure: the GenSalt study. J Hum Hypertens. 2016;30:543–8.

    Article  CAS  PubMed  Google Scholar 

  90. Liu Z, Qi H, Liu B, Liu K, Wu J, Cao H, et al. Genetic susceptibility to salt-sensitive hypertension in a Han Chinese population: a validation study of candidate genes. Hypertens Res. 2017;40:876–84.

    Article  CAS  PubMed  Google Scholar 

  91. Liu F, Zheng S, Mu J, Chu C, Wang L, Wang Y, et al. Common variation in with no-lysine kinase 1 (WNK1) and blood pressure responses to dietary sodium or potassium interventions—family-based association study. Circ J. 2013;77:169–74.

    Article  CAS  PubMed  Google Scholar 

  92. Toda N, Arakawa K. Salt-induced hemodynamic regulation mediated by nitric oxide. J Hypertens. 2011;29:415–24.

    Article  CAS  PubMed  Google Scholar 

  93. Dengel DR, Brown MD, Ferrell RE, Reynolds TH, Supiano MA. A preliminary study on T-786C endothelial nitric oxide synthase gene and renal hemodynamic and blood pressure responses to dietary sodium. Physiol Res. 2007;56:393–401.

    CAS  PubMed  Google Scholar 

  94. Miyaki K, Tohyama S, Murata M, Kikuchi H, Takei I, Watanabe K, et al. Salt intake affects the relation between hypertension and the T-786C polymorphism in the endothelial nitric oxide synthase gene. Am J Hypertens. 2005;18:1556–62.

    Article  CAS  PubMed  Google Scholar 

  95. Castejon AM, Bracero J, Hoffmann IS, Alfieri AB, Cubeddu LX. NAD(P)H oxidase p22phox gene C242T polymorphism, nitric oxide production, salt sensitivity and cardiovascular risk factors in Hispanics. J Hum Hypertens. 2006;20:772–9.

    Article  CAS  PubMed  Google Scholar 

  96. Shindo T, Kurihara H, Maemura K, Kurihara Y, Ueda O, Suzuki H, et al. Renal damage and salt-dependent hypertension in aged transgenic mice overexpressing endothelin-1. J Mol Med. 2002;80:105–16.

    Article  CAS  PubMed  Google Scholar 

  97. Caprioli J, Mele C, Mossali C, Gallizioli L, Giacchetti G, Noris M, et al. Polymorphisms of EDNRB, ATG, and ACE genes in salt-sensitive hypertension. Can J Physiol Pharmacol Can. 2008;86:505–10.

    Article  CAS  Google Scholar 

  98. Rhee M-Y, Yang SJ, Oh SW, Park Y, Kim C, Park H-K, et al. Novel genetic variations associated with salt sensitivity in the Korean population. Hypertens Res. 2011;34:606–11.

    Article  CAS  PubMed  Google Scholar 

  99. Manosroi W, Tan JW, Rariy CM, Sun B, Goodarzi MO, Saxena AR, et al. The association of estrogen receptor-beta gene variation with salt-sensitive blood pressure. J Clin Endocrinol Metab. 2017;102:4124–35.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Defagó MD, Gu D, Hixson JE, Shimmin LC, Rice TK, Gu CC, et al. Common genetic variants in the endothelial system predict blood pressure response to sodium intake: the GenSalt study. Am J Hypertens. 2013;26:643–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Han X, Hu Z, Chen J, Huang J, Huang C, Liu F, et al. Associations between genetic variants of nadph oxidase-related genes and blood pressure responses to dietary sodium intervention: the GenSalt study. Am J Hypertens. 2017;30:427–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Kedzierska K. Activity of the sodium-proton exchanger and polymorphism of G-protein beta-3 subunit in patients with essential hypertension. Ann Acad Med Stetin. 2004;50:75–86.

    CAS  PubMed  Google Scholar 

  103. Schorr U, Blaschke K, Beige J, Distler A, Sharma AM. G-protein beta3 subunit 825T allele and response to dietary salt in normotensive men. J Hypertens. 2000;18:855–9.

    Article  CAS  PubMed  Google Scholar 

  104. Beeks E, Kessels AGH, Kroon AA, van der Klauw MM, de Leeuw PW. Genetic predisposition to salt-sensitivity: a systematic review. J Hypertens. 2004;22:1243–9.

    Article  CAS  PubMed  Google Scholar 

  105. Barlassina C, Schork NJ, Manunta P, Citterio L, Sciarrone M, Lanella G, et al. Synergistic effect of alpha-adducin and ACE genes causes blood pressure changes with body sodium and volume expansion. Kidney Int. 2000;57:1083–90.

    Article  CAS  PubMed  Google Scholar 

  106. Cusi D, Barlassina C, Azzani T, Casari G, Citterio L, Devoto M, et al. Polymorphisms of alpha-adducin and salt sensitivity in patients with essential hypertension. Lancet. 1997;349:1353–7.

    Article  CAS  PubMed  Google Scholar 

  107. Glorioso N, Manunta P, Filigheddu F, Troffa C, Stella P, Barlassina C, et al. The role of alpha-adducin polymorphism in blood pressure and sodium handling regulation may not be excluded by a negative association study. Hypertension. 1999;34:649–54.

    Article  CAS  PubMed  Google Scholar 

  108. Grant FD, Romero JR, Jeunemaitre X, Hunt SC, Hopkins PN, Hollenberg NH, et al. Low-renin hypertension, altered sodium homeostasis, and an alpha-adducin polymorphism. Hypertension. 2002;39:191–6.

    Article  CAS  PubMed  Google Scholar 

  109. Manunta P, Cusi D, Barlassina C, Righetti M, Lanzani C, D’Amico M, et al. Alpha-adducin polymorphisms and renal sodium handling in essential hypertensive patients. Kidney Int. 1998;53:1471–8.

    Article  CAS  PubMed  Google Scholar 

  110. Manunta P, Maillard M, Tantardini C, Simonini M, Lanzani C, Citterio L, et al. Relationships among endogenous ouabain, alpha-adducin polymorphisms and renal sodium handling in primary hypertension. J Hypertens. 2008;26:914–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Sciarrone MT, Stella P, Barlassina C, Manunta P, Lanzani C, Bianchi G, et al. ACE and alpha-adducin polymorphism as markers of individual response to diuretic therapy. Hypertension. 2003;41:398–403.

    Article  CAS  PubMed  Google Scholar 

  112. Kelly TN, Rice TK, Gu D, Hixson JE, Chen J, Liu D, et al. Novel genetic variants in the alpha-adducin and guanine nucleotide binding protein beta-polypeptide 3 genes and salt sensitivity of blood pressure. Am J Hypertens. 2009;22:985–92.

    Article  CAS  PubMed  Google Scholar 

  113. Charkoudian N, Rabbitts JA. Sympathetic neural mechanisms in human cardiovascular health and disease. Mayo Clin Proc. 2009;84:822–30.

    Article  PubMed  PubMed Central  Google Scholar 

  114. Thomas P, Dasgupta I. The role of the kidney and the sympathetic nervous system in hypertension. Pediatr Nephrol. 2015;30:549–60.

    Article  PubMed  Google Scholar 

  115. Pojoga L, Kolatkar NS, Williams JS, Perlstein TS, Jeunemaitre X, Brown NJ, et al. Beta-2 adrenergic receptor diplotype defines a subset of salt-sensitive hypertension. Hypertension. 2006;48:892–900.

    Article  CAS  PubMed  Google Scholar 

  116. Sun B, Williams JS, Svetkey LP, Kolatkar NS, Conlin PR. Beta2-adrenergic receptor genotype affects the renin-angiotensin-aldosterone system response to the Dietary Approaches to Stop Hypertension (DASH) dietary pattern. Am J Clin Nutr. 2010;92:444–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Sanada H, Yatabe J, Midorikawa S, Hashimoto S, Watanabe T, Moore JH, et al. Single-nucleotide polymorphisms for diagnosis of salt-sensitive hypertension. Clin Chem. 2006;52:352–60.

    Article  CAS  PubMed  Google Scholar 

  118. Wainford RD, Carmichael CY, Pascale CL, Kuwabara JT. Galphai2-protein-mediated signal transduction: central nervous system molecular mechanism countering the development of sodium-dependent hypertension. Hypertension. 2015;65:178–86.

    Article  CAS  PubMed  Google Scholar 

  119. Zhang X, Frame AA, Williams JS, Wainford RD. GNAI2 polymorphic variance associates with salt sensitivity of blood pressure in the Genetic Epidemiology Network of Salt Sensitivity study. Physiol Genom. 2018;50:724–5.

    Article  CAS  Google Scholar 

  120. Li L, Xu J, Chen L, Jiang Z. Apelin/APJ system: a novel promising therapy target for thrombotic diseases. Acta Biochim Biophys Sin. 2016;48:589–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Li WW, Niu WQ, Zhang Y, Wu S, Gao PJ, Zhu DL. Family-based analysis of apelin and AGTRL1 gene polymorphisms with hypertension in Han Chinese. J Hypertens. 2009;27:1194–201.

    Article  CAS  PubMed  Google Scholar 

  122. Ellis KL, Newton-Cheh C, Wang TJ, Frampton CM, Doughty RN, Whalley GA, et al. Association of genetic variation in the natriuretic peptide system with cardiovascular outcomes. J Mol Cell Cardiol. 2011;50:695–701.

    Article  CAS  PubMed  Google Scholar 

  123. Widecka K, Ciechanowicz A, Adler G, Szychot E, Wodecki M, Czekalski S. Analysis of polymorphisms Sma (Hpa II) and Sca I gene precursors of atrial natriuretic peptide (ANP) in patients with essential hypertension. Pol Arch Med Wewn. 1998;100:27–34.

    CAS  PubMed  Google Scholar 

  124. Chen S, Huang J, Zhao Q, Chen J, Jaquish CE, He J, et al. Associations between genetic variants of the natriuretic peptide system and blood pressure response to dietary sodium intervention: the GenSalt study. Am J Hypertens. 2016;29:397–404.

    Article  CAS  PubMed  Google Scholar 

  125. Mei H, Gu D, Hixson JE, Rice TK, Chen J, Shimmin LC, et al. Genome-wide linkage and positional association study of blood pressure response to dietary sodium intervention: the GenSalt study. Am J Epidemiol. 2012;176(Suppl. 7):S81–90.

    Article  PubMed  PubMed Central  Google Scholar 

  126. Gu D, Zhao Q, Kelly TN, Hixson JE, Rao DC, Cao J, et al. The role of the kallikrein-kinin system genes in the salt sensitivity of blood pressure: the GenSalt study. Am J Epidemiol. 2012;176(Suppl. 7):S72–80.

    Article  PubMed  PubMed Central  Google Scholar 

  127. Eap CB, Bochud M, Elston RC, Bovet P, Maillard MP, Nussberger J, et al. CYP3A5 and ABCB1 genes influence blood pressure and response to treatment, and their effect is modified by salt. Hypertension. 2007;49:1007–14.

    Article  CAS  PubMed  Google Scholar 

  128. Bochud M, Eap CB, Elston RC, Bovet P, Maillard M, Schild L, et al. Association of CYP3A5 genotypes with blood pressure and renal function in African families. J Hypertens. 2006;24:923–9.

    Article  CAS  PubMed  Google Scholar 

  129. Ho H, Pinto A, Hall SD, Flockhart DA, Li L, Skaar TC, et al. Association between the CYP3A5 genotype and blood pressure. Hypertension. 2005;45:294–8.

    Article  CAS  PubMed  Google Scholar 

  130. Yagil C, Hubner N, Monti J, Schulz H, Sapojnikov M, Luft FC, et al. Identification of hypertension-related genes through an integrated genomic-transcriptomic approach. Circ Res. 2005;96:617–25.

    Article  CAS  PubMed  Google Scholar 

  131. Tian Z, Greene AS, Usa K, Matus IR, Bauwens J, Pietrusz JL, et al. Renal regional proteomes in young Dahl salt-sensitive rats. Hypertension. 2008;51:899–904.

    Article  CAS  PubMed  Google Scholar 

  132. Havlik RJ. Predictors of hypertension. Popul Stud Am J Hypertens. 1991;4:586S–589S.

    Article  CAS  Google Scholar 

  133. Castrop H, Kurtz A. Differential nNOS gene expression in salt-sensitive and salt-resistant Dahl rats. J Hypertens. 2001;19:1223–31.

    Article  CAS  PubMed  Google Scholar 

  134. Fava C, Danese E, Montagnana M, Sjogren M, Almgren P, Engstrom G, et al. Serine/threonine kinase 39 is a candidate gene for primary hypertension especially in women: results from two cohort studies in Swedes. J Hypertens. 2011;29:484–91.

    Article  CAS  PubMed  Google Scholar 

  135. Garza AE, Rariy CM, Sun B, Williams J, Lasky-Su J, Baudrand R, et al. Variants in striatin gene are associated with salt-sensitive blood pressure in mice and humans. Hypertension. 2015;65:211–7.

    Article  CAS  PubMed  Google Scholar 

  136. He J, Kelly TN, Zhao Q, Li H, Huang J, Wang L, et al. Genome-wide association study identifies 8 novel loci associated with blood pressure responses to interventions in Han Chinese. Circ Cardiovasc Genet. 2013;6:598–607.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Muller DN, Dechend R, Mervaala EM, Park JK, Schmidt F, Fiebeler A, et al. NF-kappaB inhibition ameliorates angiotensin II-induced inflammatory damage in rats. Hypertension. 2000;35:193–201.

    Article  CAS  PubMed  Google Scholar 

  138. Rodríguez-Iturbe B, Ferrebuz A, Vanegas V, Quiroz Y, Mezzano S, Vaziri ND. Early and sustained inhibition of nuclear factor-kappaB prevents hypertension in spontaneously hypertensive rats. J Pharmacol Exp Ther. 2005;315:51–57.

    Article  CAS  PubMed  Google Scholar 

  139. Goldstein DB, Allen A, Keebler J, Margulies EH, Petrou S, Petrovski S, et al. Sequencing studies in human genetics: design and interpretation. Nat Rev Genet. 2013;14:460–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Kelly TN, Li C, Hixson JE, Gu D, Rao DC, Huang J, et al. Resequencing study identifies rare renin-angiotensin-aldosterone system variants associated with blood pressure salt-sensitivity: the GenSalt study. Am J Hypertens. 2017;30:495–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Gu X, Gu D, He J, Rao DC, Hixson JE, Chen J, et al. Resequencing epithelial sodium channel genes identifies rare variants associated with blood pressure salt-sensitivity: the GenSalt study. Am J Hypertens. 2018;31:205–11.

    Article  CAS  PubMed  Google Scholar 

  142. Rayner B, Ramesar R, Steyn K, Levitt N, Lombard C, Charlton K. G-protein-coupled receptor kinase 4 polymorphisms predict blood pressure response to dietary modification in Black patients with mild-to-moderate hypertension. J Hum Hypertens. 2012;26:334–9.

    Article  CAS  PubMed  Google Scholar 

  143. Chu C, Wang Y, Ren KY, et al. Genetic variants in adiponectin and blood pressure responses to dietary sodium or potassium interventions: a family-based association study. J Hum Hypertens. 2016;30:563–70.

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Acknowledgements

Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number P20GM109036. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. YL is supported by a research training grant (D43TW009107) from the National Institutes of Health John E. Fogarty International Center, Bethesda, Maryland.

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Liu, Y., Shi, M., Dolan, J. et al. Sodium sensitivity of blood pressure in Chinese populations. J Hum Hypertens 34, 94–107 (2020). https://doi.org/10.1038/s41371-018-0152-0

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