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Lack of association between the G protein β3 subunit gene and essential hypertension in Chinese: a case-control and a family-based study

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Abstract

A C825T polymorphism of the gene encoding the G protein β3 subunit (GNB3) is associated with enhanced G protein activity and increased intracellular signal transduction. The 825T allele has been implicated in the development of hypertension in some ethnic groups, especially in whites. Studies in Asians and blacks are more controversial, and little information is available on this polymorphism in the susceptibility to hypertension in the Chinese population. Furthermore, the inconsistency between studies may be due to genetic heterogeneity of the population selected and/or the lack of statistical power. We investigated the relationship of this polymorphism with hypertension in two independent northern Chinese populations using both a case-control and a family-based study design. The GNB3 C825T polymorphism was determined by polymerase chain reaction and restriction enzyme digestion. In the case-control study which included 585 hypertensive case subjects and 580 normotensive control subjects there was no significant association between the polymorphism and hypertension status or blood pressure levels. The lack of association was confirmed by the results obtained in 181 hypertensive families using both transmission disequilibrium test and sib transmission disequilibrium test. No preferential transmission was observed for the GNB3 825T allele to the affected subjects. Furthermore, there was no significant association between the polymorphism and body mass index in the case-control study. Therefore our work does not provide evidence in favor of GNB3 C825T being a candidate gene for conferring genetic susceptibility to hypertension or obesity in northern Chinese population.

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Abbreviations

TDT:

Transmission/disequilibrium test

References

  1. Carretero OA, Oparil S (2000) Essential hypertension. Circulation 101:329–335

    CAS  PubMed  Google Scholar 

  2. Gu D, Reynolds K, Wu X, Chen J, Duan X, Muntner P, Huang G, Reynolds RF, Su S, Whelton PK, He J (2002) Prevalence, awareness, treatment, and control of hypertension in China. Hypertension 40:920–927

    Article  CAS  PubMed  Google Scholar 

  3. Ward R (1995) Familial aggregation and genetic epidemiology of blood pressure. In: Laragh JH, Brenner BM (eds) Hypertension: pathophysiology, diagnosis and management. Raven, New York, pp 67–88

  4. Jeunemaitre X, Gimenez-Roqueplo A-P, Celerier J, Corvol P (1999) Angiotensinogen variants and human hypertension. Curr Hypertens Rep 1:31–41

    CAS  PubMed  Google Scholar 

  5. Siffert W, Rosskopf D, Siffert G, Busch S, Moritz A, Erbel R, Sharma A, Ritz E, Wichmann H, Jakobs KH, Horsthemke B (1998) Association of a human G-protein beta3 subunit variant with hypertension. Nat Genet 18:45–48

    CAS  PubMed  Google Scholar 

  6. Benjafield AV, Jeyasingam CL, Nyholt DR, Griffiths LR, Morris BJ. G-proteinβ3 subunit gene (GNB3) variant in causation of essential hypertension (1998) Hypertension 32:1094–1097

    CAS  PubMed  Google Scholar 

  7. Beige J, Hohenbleicher H, Distler A, Sharma A (1999) G-protein β3 subunit C825T variant and ambulatory blood pressure in essential hypertension. Hypertension 33:1049–1051

    CAS  PubMed  Google Scholar 

  8. Hengstenberg C, Schunkert H, Mayer B, Doring A, Lowel H, Hense HW, Fischer M, Riegger GA, Holmer SR (2001) Association between a polymorphism in the G protein beta 3 subunit gene (GNB3) with essential hypertension but not with myocardial infarction. Cardiovasc Res 49:820–827

    Article  CAS  PubMed  Google Scholar 

  9. Schunkert H, Hense H-W, Doring A, Riegger G, Siffert W (1998) Association between a polymorphism in the G proteinβ3 subunit gene and lower rennin and elevated diastolic blood pressure levels. Hypertension 32:510–513

    CAS  PubMed  Google Scholar 

  10. Siffert W, Forster P, Jockel K-H, Mvere DA, Brinkman B, Naber C, Crookes R, Du P Heyns A, Epplen JT, Fridey J, Freedman BI, Muller N, Stolke D, Sharma AM, Al Moutaery K, Grosse-Wilde H, Buerbaum B, Ehrlich T, Ahmad HR, Horsthemke B, Du Toit ED, Tiilikainen A, Ge J, Wang Y, Rosskopf D (1999) Worldwide ethnic distribution of the G proteinβ3 subunit 825T allele and its association with obesity in Caucasians, Chinese, and black African individuals. J Am Soc Nephrol 10:1921–1930

    CAS  PubMed  Google Scholar 

  11. Siffert W, Naber C, Walla M, Ritz E (1999) G protein β3 subunit 825T allele and its potential association with obesity in hypertensive individuals. J Hypertens 17:1–4

    CAS  PubMed  Google Scholar 

  12. Hegele RA, Anderson C, Young TK, Connelly PW (1999) G protein β3 subunit gene splice variant and body fat distribution in Nunavut Inuit. Genome Res 9:972–977

    Article  CAS  PubMed  Google Scholar 

  13. Poch E, Giner V, Gonzalez-Nunez D, Coll E, Oriola J, de la Sierra A (2002) Association of the G protein beta3 subunit T allele with insulin resistance in essential hypertension. Clin Exp Hypertens 24:345–353

    Article  CAS  PubMed  Google Scholar 

  14. Tabor HK, Myer R, Myers RM (2002) Candidate-gene approaches for studying complex genetic traits: practical considerations. Nat Rev Genet 3:1–7

    Article  Google Scholar 

  15. Lander ES, Schork NJ (1994) Genetic dissection of complex traits. Science 263:2037–2048

    Google Scholar 

  16. Spielman RS, McGinnis RE, Ewens WJ (1993) Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet 52:506–616

    PubMed  Google Scholar 

  17. Spielman RS, Ewens WJ (1998) A sibship test for linkage in the presence of association: the sib transmission/disequilibrium test. Am J Hum Genet 62:450–458

    CAS  PubMed  Google Scholar 

  18. Brand E, Herrmann S-M, Nicaud V, Ruidavets J-B, Evans A, Arveiler D, Luc G, Plouin P-F, Tiret L, Cambien F (1999) The 825T polymorphism of the G-protein subunitβ3 is not related to hypertension. Hypertension 33:1175–1178

    CAS  PubMed  Google Scholar 

  19. Snapir A, Heinonen, Tuomainen TP, Lakka TA, Kauhanen J, Sanonen JT, Scheinin M (2001) G-protein beta3 subunit C825T polymorphism: no association with risk for hypertension and obesity. J Hypertens 19:2149–2155

    Article  CAS  PubMed  Google Scholar 

  20. Larson N, Hutchinson R, Boerwinkle E (2000) Lack of association of 3 functional variants with hypertension in African Americans. Hypertension 35:1297–1300

    CAS  PubMed  Google Scholar 

  21. Dong Y, Zhu H, Sagnella GA, Carter ND, Cook DG, Cappuccio FP (1999) Association between the C825T polymorphism of the G proteinβ3-subunit gene and hypertension in blacks. Hypertension 34:1193–1196

    CAS  PubMed  Google Scholar 

  22. Kato N, Sugiyama T, Morita H, Kurihara H, Yamori Y, Yazaki Y (1998) G proteinβ3 subunit variant and essential hypertension in Japanese. Hypertension 32:935–938

    CAS  PubMed  Google Scholar 

  23. Ishikawa K, Imai Y, Katsuya T, Ohkubo T, Tsuji I, Nagai K, Takami S, Nakata Y, Satoh H, Hisamichi S, Higaki J, Ogihara T (2000) Human G-protein beta3 subunit variant is associated with serum potassium and total cholesterol levels but not with blood pressure. Am J Hypertens 13:140–145

    Article  CAS  PubMed  Google Scholar 

  24. Tsai CH, Yeh HI, Chou Y, Liu HF, Yang TY, Wang JC, Wang NM, Chang JG (2000) G protein beta3 subunit and essential hypertension in Taiwan: a case-control study. Int J Cardiol 73:191–195

    Article  CAS  PubMed  Google Scholar 

  25. Hegele RA, Harris SB, Hanley AJG, Cao H, Zinman B (1998) G protein β3 subunit gene variant and blood pressure variation in Canadian Oji-Cree. Hypertension 32:688–692

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  27. Kardia SL (2000) Context-dependent genetic effects in hypertension. Curr Hypertens Rep 2:32–38

    CAS  PubMed  Google Scholar 

  28. Felder RA, Sanada H, Xu J, Yu PY, Wang Z, Watanabe H, Asico LD, Wang W, Zheng S, Yamaguchi I, Williams SM, Gainer J, Brown NJ, Hazen-Martin D, Wong LJ, Robillard JE, Carey RM, Eisner GM, Jose PA (2002) G protein-coupled receptor kinase 4 gene variants in human essential hypertension. Proc Natl Acad Sci U S A 99:3872–3877

    Article  CAS  PubMed  Google Scholar 

  29. Williams SM, Addy JH, Phillips JA 3rd, Dai M, Kpodonu J, Afful J, Jackson H, Joseph K, Eason F, Murray MM, Epperson P, Aduonum A, Wong LJ, Jose PA, Felder RA (2000) Combinations of variations in multiple genes are associated with hypertension. Hypertension 36:2–6

    CAS  PubMed  Google Scholar 

  30. Brand E, Wang JG, Hermann SM, Staessen JA (2003) An epidemiological study of blood pressure and metabolic phenotypes in relation to the Gbeta3 C825T polymorphism. J Hypertens 21:729–737

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We gratefully acknowledge the collaboration of Max Delbruck Center in Berlin, Germany. We are deeply indebted to Prof. Klaus Lindpaintner (Roche Genetics and Roche Center for Medical Genomics) and Dr. Peter Nuernberg (Gene Mapping Center, MDC) for continuous support and invaluable help.

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Authors and Affiliations

  1. Sino-German Laboratory for Molecular Medicine, Fu Wai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences, 167 Beilishilu, 100037, Beijing, China

    Xiaohong Huang, Zhenyu Ju, Yan Song, Hongye Zhang, Kai Sun, Hongyan Lu & Rutai Hui

  2. Department of Pediatrics and Physiology and Biophysics, Georgetown University Medical Center, Washington, DC, USA

    Zhiwei Yang & Pedro A. Jose

  3. Institute of Chronic and Non-Communicable Diseases Control and Prevention, Henan Provincial Center of Anti-Epidemic and Hygiene, Henan Province, China

    Gang Zhou, Meng Wang, Weifeng Wang & Shixian Feng

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  1. Xiaohong Huang
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  2. Zhenyu Ju
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  3. Yan Song
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Correspondence to Xiaohong Huang.

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Huang, X., Ju, Z., Song, Y. et al. Lack of association between the G protein β3 subunit gene and essential hypertension in Chinese: a case-control and a family-based study. J Mol Med 81, 729–735 (2003). https://doi.org/10.1007/s00109-003-0482-3

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  • DOI: https://doi.org/10.1007/s00109-003-0482-3

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