Original Article | Published:

Association between a polymorphic poly-T repeat sequence in the promoter of the somatostatin gene and hypertension

Hypertension Research volume 39, pages 467474 (2016) | Download Citation

Abstract

Despite the numerous common pathways connecting blood pressure regulation to somatostatin (SST) metabolism, the SST gene has never been seen as a significant blood pressure modulator. The aim of this study was to evaluate the association between a poly-T repeat sequence (rs34872250) in the promoter of the SST gene and blood pressure, according to the obesity status. We genotyped 1918 French-Canadian subjects from a founder population. Analyses were performed according to the length of the poly-T repeat sequence on both alleles and divided into two groups, the 13/13–13/14 group and the 13/15–13/16 group. The effect of age, gender, body mass index, antihypertensive drugs and diabetic status were considered. Systolic, diastolic and mean blood pressures are significantly higher among the 13/15–13/16 group in the whole sample (P<0.05). Whereas the differences remain significant in women, they turn to be non-significant when men are considered alone. The risk of hypertension is increased in the 13/15–13/16 group, particularly among overweight/obese subjects. Systolic blood pressure is significantly higher among overweight/obese carriers of the 13/15–13/16 alleles in the whole sample (P<0.001), in men (P=0.006) and in women (P=0.002), even after correction for age and antihypertensive drugs. These results suggest that the poly-T repeat sequence polymorphism in the promoter of the SST gene is associated with significant variations of blood pressure and could modulate the risk of hypertension, particularly among women.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    , . Management of hypertension in the elderly. Nat Rev Cardiol 2012; 9: 286–296.

  2. 2.

    , , . Essential hypertension. Lancet 2007; 370: 591–603.

  3. 3.

    , , , , . The burden of blood pressure-related disease: a neglected priority for global health. Hypertension 2007; 50: 991–997.

  4. 4.

    , , , , , , . STK39 polymorphism is associated with essential hypertension: a systematic review and meta-analysis. PLoS ONE 2013; 8: e59584.

  5. 5.

    , , , , , , , , . Association between single-nucleotide polymorphisms in six hypertensive candidate genes and hypertension among northern Han Chinese individuals. Hypertens Res 2014; 37: 1068–1074.

  6. 6.

    , , , , , , , . Novel modalities of somatostatin actions. Eur J Endocrinol 2004; 151: 643–655.

  7. 7.

    , , , . Regulation of pancreatic somatostatin gene expression by insulin and glucagon. Mol Cell Endocrinol 2005; 235: 31–37.

  8. 8.

    , . Pharmacological rationale for the use of somatostatin and analogues in portal hypertension. Aliment Pharmacol Ther 2003; 18: 375–386.

  9. 9.

    , . Somatostatin administration modifies food intake, body weight, and gut motility in rat. Peptides 1998; 19: 991–997.

  10. 10.

    , , , , , , . Effect of somatostatin analog on high-fat diet-induced metabolic syndrome: involvement of reactive oxygen species. Peptides 31: 625–6292009.

  11. 11.

    , , , , , . Managing hyperglycemia in patients with Cushing's disease treated with pasireotide: medical expert recommendations. Pituitary 2014; 17: 180–186.

  12. 12.

    , , , , , , , , , . Octreotide: a therapeutic option for idiopathic intracranial hypertension. Neurol Neurophysiol Neurosci 2007; 10: 1.

  13. 13.

    , , , . Local arterial vasoconstriction induced by octreotide in patients with cirrhosis. Hepatology 2000; 31: 572–576.

  14. 14.

    , , , , . Impact of somatostatin analogs on the heart in acromegaly: a metaanalysis. J Clin Endocrinol Metab 2007; 92: 1743–1747.

  15. 15.

    , , , , . Effect of somatostatin versus octreotide on portal haemodynamics in patients with cirrhosis and portal hypertension. Eur J Gastroenterol Hepatol 2005; 17: 53–57.

  16. 16.

    , , , , , , , , , , . Glycerol as a correlate of impaired glucose tolerance: dissection of a complex system by use of a simple genetic trait. Am J Hum Genet 2000; 66: 1558–1568.

  17. 17.

    , , , , , , , , , , , . Molecular scanning of the human PPARa gene: association of the L162v mutation with hyperapobetalipoproteinemia. J Lipid Res 2000; 41: 945–952.

  18. 18.

    The Airlie (VA) Consensus Conference. In: Standardization of anthropometric measurements Lohman TRA, Martorel R (eds). Human Kinetics Publishers: Champaign, IL, USA. 1988, pp 39–80.

  19. 19.

    , , , , , , . Procedure to protect confidentiality of familial data in community genetics and genomic research. Clin Genet 1999; 55: 259–264.

  20. 20.

    , . Automated enzymatic standardized lipid analyses for plasma and lipoprotein fractions. Clin Chim Acta 1987; 166: 1–8.

  21. 21.

    , , . Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499–502.

  22. 22.

    , , , , , , , , . A modified formula for calculating low-density lipoprotein cholesterol values. Lipids Health Dis 2010; 9: 52.

  23. 23.

    , . A curriculum for the training and certification of blood pressure measurement for health care providers. Can J Cardiol 1995; 11 (Suppl H): 38H–42H.

  24. 24.

    , , , , , , , , , , , Council on High Blood Pressure Research P, Public Education Subcommittee AHA. Recommendations for blood pressure measurement in humans: an AHA scientific statement from the Council on High Blood Pressure Research Professional and Public Education Subcommittee. J Clin Hypertens (Greenwich) 2005; 7: 102–109.

  25. 25.

    , , , , , , , . Pulse pressure compared with other blood pressure indexes in the prediction of 25-year cardiovascular and all-cause mortality rates: The Chicago Heart Association Detection Project in Industry Study. Hypertension 2001; 38: 232–237.

  26. 26.

    , , , , . Blood pressure control and components of the metabolic syndrome: the GOOD survey. Cardiovasc Diabetol 2009; 8: 51.

  27. 27.

    , , , , . Ethical issues in molecular screening for heterozygous familial hypercholesterolemia: the complexity of dealing with genetic susceptibility to coronary artery disease. Community Genet 1999; 2: 2–8.

  28. 28.

    , , , , . Mechanisms involved in the somatostatin-induced contraction of vascular smooth muscle cells. Peptides 1999; 20: 929–935.

  29. 29.

    , , , , , , . Meta-analysis: vasoactive medications for the management of acute variceal bleeds. Aliment Pharmacol Ther 2012; 35: 1267–1278.

  30. 30.

    , , , , . Glycerol: a neglected variable in metabolic processes? Bioessays 2001; 23: 534–542.

  31. 31.

    , , , , , . Low-dose GH replacement improves the adverse lipid profile associated with the adult GH deficiency syndrome. Clin Endocrinol (Oxf) 2002; 56: 525–532.

  32. 32.

    , . Effects of growth hormone-releasing hormone on visceral fat, metabolic, and cardiovascular indices in human studies. Growth Hormone IGF Res 2015; 25: 59–65.

  33. 33.

    , , , , , , , . Regulation of somatotroph cell function by the adipose tissue. Int J Obes Relat Metab Disord 2000; 24 (Suppl 2): S100–S103.

  34. 34.

    , , . Role of endogenous somatostatin in regulating GH output under basal conditions and in response to metabolic extremes. Mol Cell Endocrinol 2008; 286: 155–168.

  35. 35.

    , , , , . Somatostatin and its receptors contribute in a tissue-specific manner to the sex-dependent metabolic (fed/fasting) control of growth hormone axis in mice. Am J Physiol Endocrinol Metab 2011; 300: E46–E54.

  36. 36.

    , . Gender-dependent role of endogenous somatostatin in regulating growth hormone-axis function in mice. Endocrinology 2007; 148: 5998–6006.

  37. 37.

    , , , . Use of somatostatin analogues in obesity. Drugs 2008; 68: 1963–1973.

  38. 38.

    , . Determinants of GH-releasing hormone and GH-releasing peptide synergy in men. Am J Physiol Endocrinol Metab 2009; 296: E1085–E1092.

  39. 39.

    , , , , , . Somatostatin dramatically stimulates growth hormone release from primate somatotrophs acting at low doses via somatostatin receptor 5 and cyclic AMP. J Neuroendocrinol 2012; 24: 453–463.

  40. 40.

    , , . Neuronostatin acts in brain to biphasically increase mean arterial pressure through sympatho-activation followed by vasopressin secretion: the role of melanocortin receptors. Am J Physiolo Regul Integr Compar Physiol 2011; 300: R1194–R1199.

  41. 41.

    , . Pressor doses of vasopressin result in only transient elevations in plasma peptide levels. Peptides 2012; 33: 342–345.

  42. 42.

    , , , , , , , , , , . Neuronostatin, a novel peptide encoded by somatostatin gene, regulates cardiac contractile function and cardiomyocyte survival. J Biol Chem 2012; 287: 4572–4580.

  43. 43.

    , , , , , , . ANTXR2 is a potential causative gene in the genome-wide association study of the blood pressure locus 4q21. Hypertens Res 2014; 37: 811–817.

  44. 44.

    , , . Candidate-gene approaches for studying complex genetic traits: practical considerations. Nat Rev Genet 2002; 3: 391–397.

  45. 45.

    , , , , . Ambulatory blood pressure monitoring: importance of sampling rate and duration—48 versus 24 hours—on the accurate assessment of cardiovascular risk. Chronobiol Int 2013; 30: 55–67.

  46. 46.

    , , , , , , , , , , , , , , , , , , , , . Identification of a chromosome 8p locus for early-onset coronary heart disease in a French Canadian population. Eur J Hum Genet 2008; 16: 105–114.

  47. 47.

    , , , , , , , , , . Replication of the top 10 most significant polymorphisms from a large blood pressure genome-wide association study of northeastern Han Chinese East Asians. Hypertens Res 2014; 37: 134–138.

  48. 48.

    . The evolutionary significance of cis-regulatory mutations. Nat Rev Genet 2007; 8: 206–216.

  49. 49.

    . Somatostatin and its receptor family. Front Neuroendocrinol 1999; 20: 157–198.

Download references

Acknowledgements

We thank all the staff of the ECOGENE-21 Clinical Research Center and Chicoutimi Hospital Lipid Clinic for their help in data collection and their dedicated work. Finally, we acknowledge the contribution of the subjects who participated in this project; without them, clinical studies would not be possible. This research was supported by ECOGENE-21, the CIHR team in community genetics (grant no. CTP-82941).

Author information

Affiliations

  1. Lipidology Unit, Community Genomic Medicine Center, Department of Medicine, Université de Montréal, Chicoutimi, Québec, Canada

    • Monique Tremblay
    • , Diane Brisson
    •  & Daniel Gaudet
  2. ECOGENE-21, Clinical and Translational Research Center, Chicoutimi, Québec, Canada

    • Monique Tremblay
    • , Diane Brisson
    •  & Daniel Gaudet

Authors

  1. Search for Monique Tremblay in:

  2. Search for Diane Brisson in:

  3. Search for Daniel Gaudet in:

Competing interests

The authors declare no conflict of interest.

Corresponding author

Correspondence to Daniel Gaudet.

About this article

Publication history

Received

Revised

Accepted

Published

DOI

https://doi.org/10.1038/hr.2016.4

Further reading