Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Meta-based association of the lipoprotein lipase gene S447X variant with hypertension and blood pressure variation

Abstract

Association of the lipoprotein lipase (LPL) gene S447X variant with hypertension has been investigated extensively, whereas the results are often irreproducible. We therefore conducted a meta-analysis to examine whether S447X variant was associated with hypertension and blood pressure variation. Case–control reports published in English language and humans were identified from MEDLINE, EMBASE and Web of Science search engines as of 10 December 2009. Fixed-effects model was applied to pool data in the absence of between-studies heterogeneity, and random-effects model otherwise. A total of five studies (960 cases and 1145 controls) for hypertension and four studies (n=2777) for blood pressure were included. Compared with 447SS homogeneous carriers, those with 447X variant had a lower risk of hypertension (odds ratio (OR)=0.78; 95% confidence interval (CI): 0.62–0.98; P=0.03), and this effect reached significance under the fixed-effects model (I2=30% and P=0.22). Similarly, compared with 447S allele carriers, those with 447X allele carriers also had a lower risk of hypertension (OR=0.79; 95% CI: 0.64–0.98; P=0.03). In case of pregnancy-induced hypertension, no significance was observed (P>0.05). As for blood pressure association, there was no significant difference between 447X variant and 447SS homogeneous carriers for both systolic and diastolic blood pressure in the whole population, even stratified by gender (P>0.05). The Egger test told no publication bias for all associations. This meta-analysis demonstrated that LPL gene S447X variant was significantly associated with hypertension and showed no obvious relation with pregnancy-induced hypertension and blood pressure variation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Jones DW, Hall JE . The national high blood pressure education program: thirty years and counting. Hypertension 2002; 39: 941–942.

    Article  Google Scholar 

  2. Izawa H, Yamada Y, Okada T, Tanaka M, Hirayama H, Yokota M . Prediction of genetic risk for hypertension. Hypertension 2003; 41: 1035–1040.

    Article  CAS  Google Scholar 

  3. Niu W, Guo X, Su Y, Qiu C . Apolipoprotein E and low-density lipoprotein receptor gene polymorphisms in dyslipidemias-associated essential hypertension. J Hum Hypertens 2007; 21: 337–339.

    Article  CAS  Google Scholar 

  4. Gigek Cde O, Chen ES, Cendoroglo MS, Ramos LR, Araujo LM, Payão SL et al. Association of lipase lipoprotein polymorphisms with myocardial infarction and lipid levels. Clin Chem Lab Med 2007; 45: 599–604.

    PubMed  Google Scholar 

  5. Izar MC, Helfenstein T, Ihara SS, Relvas WG, Santos AO, Fischer SC et al. Association of lipoprotein lipase D9N polymorphism with myocardial infarction in type 2 diabetes: the genetics, outcomes, and lipids in type 2 diabetes (GOLD) study. Atherosclerosis 2009; 204: 165–170.

    Article  CAS  Google Scholar 

  6. Parfenov MG, Nikolaeva TY, Sudomoina MA, Fedorova SA, Guekht AB, Gusev EI et al. Polymorphism of apolipoprotein E (APOE) and lipoprotein lipase (LPL) genes and ischaemic stroke in individuals of Yakut ethnicity. J Neurol Sci 2007; 255: 42–49.

    Article  CAS  Google Scholar 

  7. Yang Y, Mu Y, Zhao Y, Liu X, Zhao L, Wang J et al. Genetic screening of the lipoprotein lipase gene for mutations in Chinese subjects with or without hypertriglyceridemia. J Genet Genomics 2007; 34: 381–391.

    Article  CAS  Google Scholar 

  8. Ng MC, Baum L, So WY, Lam VK, Wang Y, Poon E et al. Association of lipoprotein lipase S447X, apolipoprotein E exon 4, and apoC3 -455T>C polymorphisms on the susceptibility to diabetic nephropathy. Clin Genet 2006; 70: 20–28.

    Article  CAS  Google Scholar 

  9. Bernard N, Girouard J, Forest JC, Giguère Y . The combination of ApoCIII, hepatic lipase and hormono sensitive lipase gene polymorphisms suggests an association with susceptibility to gestational hypertension. J Hum Genet 2007; 52: 244–254.

    Article  CAS  Google Scholar 

  10. Liu A, Lee L, Zhan S, Cao W, Lv J, Guo X et al. The S447X polymorphism of the lipoprotein lipase gene is associated with lipoprotein lipid and blood pressure levels in Chinese patients with essential hypertension. J Hypertens 2004; 22: 1503–1509.

    Article  CAS  Google Scholar 

  11. Hata A, Robertson M, Emi M, Lalouel JM . Direct detection and automated sequencing of individual alleles after electrophoretic strand separation: identification of a common nonsense mutation in exon 9 of the human lipoprotein lipase gene. Nucleic Acids Res 1990; 18: 5407–5411.

    Article  CAS  Google Scholar 

  12. Henderson HE, Kastelein JJ, Zwinderman AH, Gagné E, Jukema JW, Reymer PW et al. Lipoprotein lipase activity is decreased in a large cohort of patients with coronary artery disease and is associated with changes in lipids and lipoproteins. J Lipid Res 1999; 40: 735–743.

    CAS  PubMed  Google Scholar 

  13. Yang W, Huang J, Ge D, Yao C, Duan X, Shen Y et al. Lipoprotein lipase gene is in linkage with blood pressure phenotypes in Chinese pedigrees. Hum Genet 2004; 115: 8–12.

    Article  CAS  Google Scholar 

  14. Yang W, Huang J, Yao C, Su S, Liu D, Ge D et al. Linkage and linkage disequilibrium analysis of the lipoprotein lipase gene with lipid profiles in Chinese hypertensive families. Clin Sci (Lond) 2005; 108: 137–142.

    Article  CAS  Google Scholar 

  15. Sass C, Herbeth B, Siest G, Visvikis S . Lipoprotein lipase (C/G)447 polymorphism and blood pressure in the Stanislas Cohort. J Hypertens 2000; 18: 1775–1781.

    Article  CAS  Google Scholar 

  16. Clee SM, Loubser O, Collins J, Kastelein JJ, Hayden MR . The LPL S447X cSNP is associated with decreased blood pressure and plasma triglycerides, and reduced risk of coronary artery disease. Clin Genet 2001; 60: 293–300.

    Article  CAS  Google Scholar 

  17. Salah A, Khan M, Esmail N, Habibullah S, Al Lahham Y . Genetic polymorphism of S447X lipoprotein lipase (LPL) and the susceptibility to hypertension. J Crit Care 2009; 24: e11–e14.

    Article  Google Scholar 

  18. Li B, Ge D, Wang Y, Zhao W, Zhou X, Gu D et al. Lipoprotein lipase gene polymorphisms and blood pressure levels in the Northern Chinese Han population. Hypertens Res 2004; 27: 373–378.

    Article  CAS  Google Scholar 

  19. Kobashi G . Genetic and environmental factors associated with the development of hypertension in pregnancy. J Epidemiol 2006; 16: 1–8.

    Article  Google Scholar 

  20. Lau J, Ioannidis JP, Schmid CH . Quantitative synthesis in systematic reviews. Ann Intern Med 1997; 127: 820–826.

    Article  CAS  Google Scholar 

  21. Higgins JP, Thompson SG, Deeks JJ, Altman DG . Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557–560.

    Article  Google Scholar 

  22. Wittrup HH, Tybjaerg-Hansen A, Nordestgaard BG . Lipoprotein lipase mutations, plasma lipids and lipoproteins, and risk of ischemic heart disease. A meta-analysis. Circulation 1999; 99: 2901–2907.

    Article  CAS  Google Scholar 

  23. Turner ST, Chapman AB, Schwartz GL, Boerwinkle E . Effects of endothelial nitric oxide synthase, alpha-adducin, and other candidate gene polymorphisms on blood pressure response to hydrochlorothiazide. Am J Hypertens 2003; 16: 834–839.

    Article  CAS  Google Scholar 

  24. Kokubo Y, Tomoike H, Tanaka C, Banno M, Okuda T, Inamoto N et al. Association of sixty-one non-synonymous polymorphisms in forty-one hypertension candidate genes with blood pressure variation and hypertension. Hypertens Res 2006; 29: 611–619.

    Article  CAS  Google Scholar 

  25. Ma YQ, Thomas GN, Critchley JA, Lee ZS, Chan JC, Tomlinson B . Association of the D8S282 marker near the lipoprotein lipase gene locus with systolic blood pressure in healthy Chinese subjects. J Hypertens 2002; 20: 2199–2204.

    Article  CAS  Google Scholar 

  26. Tu X, Tu J, Wen X, Wang J, Zhang D . A study of lipoprotein lipase gene intron 8 polymorphisms in Chinese Han race essential hypertension patients. Int J Cardiol 2005; 99: 263–267.

    Article  Google Scholar 

  27. Das B, Pawar N, Saini D, Seshadri M . Genetic association study of selected candidate genes (ApoB, LPL, Leptin) and telomere length in obese and hypertensive individuals. BMC Med Genet 2009; 10: 99.

    Article  Google Scholar 

  28. Hunt SC, Province MA, Atwood LD, Sholinsky P, Lalouel JM, Rao DC et al. No linkage of the lipoprotein lipase locus to hypertension in Caucasians. J Hypertens 1999; 17: 39–43.

    Article  CAS  Google Scholar 

  29. Yang WJ, Huang JF, Yao CL, Fan ZJ, Ge DL, Gan WQ et al. Evidence for linkage and association of the markers near the LPL gene with hypertension in Chinese families. J Med Genet 2003; 40: e57.

    Article  CAS  Google Scholar 

  30. Chen P, Jou YS, Fann CS, Chen JW, Chung CM, Lin CY et al. Lipoprotein lipase variants associated with an endophenotype of hypertension: hypertension combined with elevated triglycerides. Hum Mutat 2009; 30: 49–55.

    Article  Google Scholar 

  31. Chen P, Jou YS, Fann CS, Chen JW, Wu SY, Pan WH . Lipoprotein lipase gene is linked and associated with hypertension in Taiwan young-onset hypertension genetic study. J Biomed Sci 2005; 12: 651–658.

    Article  CAS  Google Scholar 

  32. Talmud PJ, Flavell DM, Alfakih K, Cooper JA, Balmforth AJ, Sivananthan M et al. The lipoprotein lipase gene serine 447 stop variant influences hypertension-induced left ventricular hypertrophy and risk of coronary heart disease. Clin Sci (Lond) 2007; 112: 617–624.

    Article  CAS  Google Scholar 

  33. Ames RP . Hyperlipidemia in hypertension: causes and prevention. Am Heart J 1991; 122: 1219–1224.

    Article  CAS  Google Scholar 

  34. Ruixing Y, Jinzhen W, Weixiong L, Yuming C, Dezhai Y, Shangling P . The environmental and genetic evidence for the association of hyperlipidemia and hypertension. J Hypertens 2009; 27: 251–258.

    Article  Google Scholar 

  35. Kozaki K, Gotoda T, Kawamura M, Shimano H, Yazaki Y, Ouchi Y et al. Mutational analysis of human lipoprotein lipase by carboxy-terminal truncation. J Lipid Res 1993; 34: 1765–1772.

    CAS  PubMed  Google Scholar 

  36. Henderson HE, Kastelein JJ, Zwinderman AH, Gagné E, Jukema JW, Reymer PW et al. Lipoprotein lipase activity is decreased in a large cohort of patients with coronary artery disease and is associated with changes in lipids and lipoproteins. J Lipid Res 1999; 40: 735–743.

    CAS  PubMed  Google Scholar 

  37. Kobashi G, Hata A, Ohta K, Yamada H, Kato EH, Minakami H et al. A1166C variant of angiotensin II type 1 receptor gene is associated with severe hypertension in pregnancy independently of T235 variant of angiotensinogen gene. J Hum Genet 2004; 49: 182–186.

    Article  CAS  Google Scholar 

  38. Hirschhorn JN, Lohmueller K, Byrne E, Hirschhorn K . A comprehensive review of genetic association studies. Genet Med 2002; 4: 45–61.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was financially supported by the Seed Foundation of Development on Science and Technology by President of Capital Medical University Affiliated Beijing Anzhen Hospital (2010Z10), the Shanghai ‘Chen Guang’ Project (09CG12), the Natural Science Foundation of Shanghai (09ZR1426200), two Excellent Young Teachers Programs, one from Ruijin Hospital and the other from Shanghai City, the Science Fund of Shanghai Jiaotong University School of Medicine (09XJ21019), and the National Science Foundation for Young Scientists of China (Grant number: 30900808).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to W-Q Niu or Y Qi.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Niu, WQ., Qi, Y. Meta-based association of the lipoprotein lipase gene S447X variant with hypertension and blood pressure variation. J Hum Hypertens 25, 383–390 (2011). https://doi.org/10.1038/jhh.2010.68

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jhh.2010.68

Keywords

Search

Quick links