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Interaction between the C(-344)T polymorphism of CYP11B2 and alcohol consumption on the risk of essential hypertension in a Chinese Mongolian population

  • GENETIC EPIDEMIOLOGY
  • Published:
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Abstract

The present study aimed to explore gene–gene and gene-environment interactions among three candidate genes and several environmental risk factors, and their impacts on hypertension in Chinese Mongolian population. A cross-sectional study was conducted in 2003–2004 among 1,575 Mongolian people in Tongliao City of Inner Mongolia, China. Epidemiologic and clinical data and blood samples were obtained from subjects. Multifactor dimensionality reduction (MDR) and logistic regression were used to analyze gene–gene and gene-environment interactions. The MDR model indicated a significant interactions among the CYP11B2 gene C(-344)T polymorphism, body mass index, age, and alcohol consumption on the risk of hypertension, with a cross-validation consistency of 10 of 10 and a prediction error of 34% (P < 0.001). Logistic regression suggested alcohol consumption (≥200 g/d) was associated with an OR of 2.4 (95% CI, 1.6–3.5) for hypertension. When stratified by the CYP11B2 genotype, the estimated OR was 1.2 (95% CI, 0.5–3.0) on hypertension for the CC genotype group, but was 3.0 (95% CI, 1.5–5.7) and 2.9 (95% CI, 1.4–5.7) for the TC and TT genotype groups, respectively. A significant interaction between the CYP11B2 genotype and alcohol consumption was also found by the logistic models (P crude = 0.035, P adjusted = 0.048). This study demonstrates a significant interaction between the CYP11B2 genotype and alcohol consumption on the risk of hypertension in Chinese Mongolian population.

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Abbreviations

ACE:

Angiotensin converting enzyme

BMI:

Body mass index

DBP:

Diastolic blood pressure

eNOS:

Endothelial nitric oxide synthase

MDR:

Multifactor dimensionality reduction

PCR:

Polymerase chain reaction

RAAS:

Renin-angiotensin-aldosterone system

SBP:

Systolic blood pressure

WC:

Waist circumference

References

  1. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005;365:217–23.

    PubMed  Google Scholar 

  2. He J, Gu D, Wu X, Reynolds K, Duan X, Yao C, et al. Major causes of death among men and women in China. N Engl J Med. 2005;353:1124–34.

    Article  CAS  PubMed  Google Scholar 

  3. Pausova Z, Tremblay J, Hamet P. Gene-environment interactions in hypertension. Curr Hypertens Rep. 1999;1:42–50.

    Article  CAS  PubMed  Google Scholar 

  4. Morise T, Takeuchi Y, Takeda R. Angiotensin-converting enzyme polymorphism and essential hypertension. Lancet. 1994;343:125.

    Article  CAS  PubMed  Google Scholar 

  5. Chiang FT, Lai ZP, Chern TH, Tseng CD, Hsu KL, Lo HM, et al. Lack of association of the angiotensin converting enzyme polymorphism with essential hypertension in a Chinese population. Am J Hypertens. 1997;10:197.

    Article  CAS  PubMed  Google Scholar 

  6. Patkar S, Charita BH, Ramesh C, Padma T. High risk of essential hypertension in males with intron 4 VNTR polymorphism of eNOS gene. Indian J Hum Genet. 2010;15:49.

    Google Scholar 

  7. Qi Z, Shao-yong SU, Shu-feng C, Biao LI, Dong-feng GU. Association study of the endothelial nitric oxide synthase gene polymorphisms with essential hypertension in northern Han Chinese. Chin Med J. 2006;119:1065–71.

    Google Scholar 

  8. Hlubocka Z, Jachymova M, Heller S, Umnerova V, Danzig VV, Lanska V, et al. Association of the -344T/C aldosterone synthase gene variant with essential hypertension. Physiol Res. 2009;58:785–792.

    CAS  PubMed  Google Scholar 

  9. Casiglia E, Tikhonoff V, Mazza A, Rynkiewicz A, Limon J, Caffi S, et al. C-344T polymorphism of the aldosterone synthase gene and blood pressure in the elderly: a population-based study. [see comment]. J Hypertens. 2005;23:1991–6.

    Article  CAS  PubMed  Google Scholar 

  10. Sookoian S, Gianotti TF, Gonzalez CD, Pirola CJ. Association of the C-344T aldosterone synthase gene variant with essential hypertension: a meta-analysis. J Hypertens. 2007;25:5–13.

    Article  CAS  PubMed  Google Scholar 

  11. Tang W, Wu H, Zhou X, Cheng B, Dong Y, He L, et al. Association of the C-344T polymorphism of CYP11B2 gene with essential hypertension in Hani and Yi minorities of China. Clin Chim Acta. 2006;364:222–5.

    Article  CAS  PubMed  Google Scholar 

  12. Xu X-j, Wang S-z, Lin R-y, Wang X-f, Liang X-h, Wen H, et al. Association of the T(-344)C polymorphism of aldosterone synthase gene CYP11B2 with essential hypertension in Xinjiang Kazakh isolated group. Chung-Hua i Hsueh i Chuan Hsueh Tsa Chih. 2004;21:622–4.

    CAS  PubMed  Google Scholar 

  13. Tsujita Y, Iwai N, Katsuya T, Higaki J, Ogihara T, Tamaki S, et al. Lack of association between genetic polymorphism of CYP11B2 and hypertension in Japanese: the Suita Study. Hypertens Res Clin Exp. 2001;24:105–9.

    Article  CAS  Google Scholar 

  14. Kato N, Sugiyama T, Morita H, Kurihara H, Furukawa T, Isshiki T, et al. Comprehensive analysis of the renin-angiotensin gene polymorphisms with relation to hypertension in the Japanese. J Hypertens. 2000;18:1025–32.

    Article  CAS  PubMed  Google Scholar 

  15. Moore JH, Williams SM. New strategies for identifying gene-gene interactions in hypertension. Ann Med. 2002;34:88–95.

    Article  CAS  PubMed  Google Scholar 

  16. Hahn L, Ritchie M, Moore J. Multifactor dimensionality reduction software for detecting gene-gene and gene-environment interactions. Bioinformatics. 2003;19:376–382.

    Article  CAS  PubMed  Google Scholar 

  17. Williams SM, Ritchie MD, Phillips Iii JA, Dawson E, Prince M, Dzhura E, et al. Multilocus analysis of hypertension: a hierarchical approach. Hum Hered. 2004;57:28–38.

    Article  PubMed  Google Scholar 

  18. Cho YM, Ritchie MD, Moore JH, Park JY, Lee KU, Shin HD, et al. Multifactor-dimensionality reduction shows a two-locus interaction associated with Type 2 diabetes mellitus. Diabetologia. 2004;47:549–54.

    Article  CAS  PubMed  Google Scholar 

  19. Tsai CT, Lai LP, Lin JL, Chiang FT, Hwang JJ, Ritchie MD, et al. Renin-angiotensin system gene polymorphisms and atrial fibrillation. Circulation. 2004;109:1640.

    Article  CAS  PubMed  Google Scholar 

  20. Coffey CS, Hebert PR, Ritchie MD, Krumholz HM, Gaziano JM, Ridker PM, et al. An application of conditional logistic regression and multifactor dimensionality reduction for detecting gene-gene interactions on risk of myocardial infarction: the importance of model validation. BMC Bioinformatics. 2004;5:49.

    Article  PubMed  Google Scholar 

  21. Chan IHS, Leung TF, Tang NLS, Li CY, Sung YM, Wong GWK, et al. Gene-gene interactions for asthma and plasma total IgE concentration in Chinese children. J Allergy Clin Immunol. 2006;117:127–33.

    Article  CAS  PubMed  Google Scholar 

  22. Bei-Fan Z. Predictive values of body mass index and waist circumference for risk factors of certain related diseases in Chinese adults: study on optimal cut-off points of body mass index and waist circumference in Chinese adults. Asia Pac J Clin Nutr. 2002;11:685–93.

    Article  Google Scholar 

  23. Gustincich S, Manfioletti G, Del Sal G, Schneider C, Carninci P. A fast method for high-quality genomic DNA extraction from whole human blood. Biotechniques. 1991;11:298.

    CAS  PubMed  Google Scholar 

  24. Rigat B, Hubert C, Corvol P, Soubrier R. PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidyl carboxypeptidase 1). Nucleic Acids Res. 1992;20:1433.

    Article  CAS  PubMed  Google Scholar 

  25. Kupari M, Hautanen A, Lankinen L, Koskinen P, Virolainen J, Nikkila H, et al. Associations between human aldosterone synthase (CYP11B2) gene polymorphisms and left ventricular size, mass, and function. Am Heart Assoc. 1998;97:569–75.

    CAS  Google Scholar 

  26. Ritchie M, Hahn L, Roodi N, Bailey L, Dupont W, Parl F, et al. Multifactor-dimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer. Am J Hum Genet. 2001;69:138–47.

    Article  CAS  PubMed  Google Scholar 

  27. Ritchie MD, Hahn LW. Power of multifactor dimensionality reduction for detecting gene-gene interactions in the presence of genotyping error, missing data, phenocopy, and genetic heterogeneity. Genet Epidemiol. 2003;24:150–7.

    Article  PubMed  Google Scholar 

  28. Heidema A, Feskens E, Doevendans P, Ruven H, van Houwelingen H, Mariman E, et al. Analysis of multiple SNPs in genetic association studies: comparison of three multi-locus methods to prioritize and select SNPs. Genet Epidemiol. 2007;31:910.

    Article  PubMed  Google Scholar 

  29. Davies E, Holloway CD, Ingram MC, Inglis GC, Friel EC, Morrison C, et al. Aldosterone excretion rate and blood pressure in essential hypertension are related to polymorphic differences in the aldosterone synthase gene CYP11B2. Hypertension. 1999;33:703–7.

    CAS  PubMed  Google Scholar 

  30. Brand E, Chatelain N, Mulatero P, Fery I, Curnow K, Jeunemaitre X, et al. Structural analysis and evaluation of the aldosterone synthase gene in hypertension. Hypertension. 1998;32:198–204.

    CAS  PubMed  Google Scholar 

  31. Russo P, Siani A, Venezia A, Iacone R, Russo O, Barba G, et al. Interaction between the C (-344) T polymorphism of CYP11B2 and age in the regulation of blood pressure and plasma aldosterone levels: cross-sectional and longitudinal findings of the Olivetti Prospective Heart Study. J Hypertens. 2002;20:1785.

    Article  CAS  PubMed  Google Scholar 

  32. Zhu H, Sagnella GA, Dong Y, Miller MA, Onipinla A, Markandu ND, et al. Contrasting associations between aldosterone synthase gene polymorphisms and essential hypertension in blacks and in whites. J Hypertens. 2003;21:87–95.

    Article  CAS  PubMed  Google Scholar 

  33. Manuguerra M, Matullo G, Veglia F, Autrup H, Dunning AM, Garte S, et al. Multi-factor dimensionality reduction applied to a large prospective investigation on gene-gene and gene-environment interactions. Carcinogenesis. 2007;28:414.

    Article  CAS  PubMed  Google Scholar 

  34. MacMahon S. Alcohol consumption and hypertension. Hypertension. 1987;9:111.

    CAS  PubMed  Google Scholar 

  35. Valentino R, Tommaselli AP, Savastano S, Stewart PM, Ghiggi MR, Galletti F, et al. Alcohol inhibits 11-beta-hydroxysteroid dehydrogenase activity in rat kidney and liver. Horm Res. 1995;43:176–80.

    Article  CAS  PubMed  Google Scholar 

  36. White PC. Defects in cortisol metabolism causing low-renin hypertension. Endocr Res. 1991;17:85–107.

    Article  CAS  PubMed  Google Scholar 

  37. Miyamori I, Yasuhara S, Ikeda M, Koshida H, Takeda Y, Morise T, et al. Participation of vascular prostacyclin for the pathogenesis of experimental glucocorticoid hypertension in rats. Clin Exp Hypertens Part A Theory Pract. 1985;7:513–24.

    Article  CAS  Google Scholar 

  38. Fardella CE, Miller WL. Molecular biology of mineralocorticoid metabolism. Annu Rev Nutr. 1996;16:443–70.

    Article  CAS  PubMed  Google Scholar 

  39. Mariniello B, Ronconi V, Sardu C, Pagliericcio A, Galletti F, Strazzullo P, et al. Analysis of the 11beta-hydroxysteroid dehydrogenase type 2 gene (HSD11B2) in human essential hypertension. Am J Hypertens. 2005;18:1091–8.

    Article  CAS  PubMed  Google Scholar 

  40. Ferrari P, Krozowski Z. Role of the 11beta-hydroxysteroid dehydrogenase type 2 in blood pressure regulation. Kidney Int. 2000;57:1374–81.

    Article  CAS  PubMed  Google Scholar 

  41. Carvajal CA, Romero DG, Mosso LM, Gonzalez AA, Campino C, Montero J, et al. Biochemical and genetic characterization of 11 beta-hydroxysteroid dehydrogenase type 2 in low-renin essential hypertensives. J Hypertens. 2005;23:71–7.

    Article  CAS  PubMed  Google Scholar 

  42. Alzamora R, Michea L, Marusic ET. Role of 11beta-hydroxysteroid dehydrogenase in nongenomic aldosterone effects in human arteries. Hypertension. 2000;35:1099–104.

    CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (grant number 30360094). We are deeply appreciative of the participants in the study, and the Tongliao City centre for disease prevention and Control for their support and assistance.

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Authors and Affiliations

  1. Department of Epidemiology, Suzhou University School of Radiation Medicine and Public Health, 215123, Suzhou, China

    Xing-Qiang Pan, Yong-Hong Zhang & Wei-Jun Tong

  2. Ningbo Municipal Center for Disease Prevention and Control, Ningbo, China

    Xing-Qiang Pan

  3. Tongliao Center for Disease Prevention and Control, Tongliao, Inner Mongolia, China

    Yong-Yue Liu

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  1. Xing-Qiang Pan
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Correspondence to Wei-Jun Tong.

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Pan, XQ., Zhang, YH., Liu, YY. et al. Interaction between the C(-344)T polymorphism of CYP11B2 and alcohol consumption on the risk of essential hypertension in a Chinese Mongolian population. Eur J Epidemiol 25, 813–821 (2010). https://doi.org/10.1007/s10654-010-9504-y

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  • DOI: https://doi.org/10.1007/s10654-010-9504-y

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