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Strong association of methylenetetrahydrofolate reductase gene C677T polymorphism with hypertension and hypertension-in-pregnancy in Chinese: a meta-analysis

Journal of Human Hypertension volume 26, pages 259–267 (2012)Cite this article

Abstract

Attempts to associate methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with hypertension have been extensively evaluated, but mostly in Caucasians. We therefore meta-analysed this polymorphism in association with hypertension and hypertension-in-pregnancy (HIP) among Chinese subjects. A random-effects model was applied irrespective of between-study heterogeneity, which was evaluated by subgroup and meta-regression analyses. Study quality was assessed in duplicate. Publication bias was weighed using Egger's test and funnel plot. Data on 20 qualified studies totalling 4461 Chinese subjects were meta-analysed. In overall allelic/genotypic models, carriers of 677T or 677TT were consistently at significantly increased risk of developing hypertension and HIP. No between-study heterogeneity was identified for all genetic models, with the exception for contrast of allele 677T versus 677C in hypertension association studies (P=0.03), and the dominant contrast in HIP association studies (P=0.025). Both the subgroup and meta-regression analyses indicated that study design was a potential source of between-study heterogeneity. Funnel plot and Egger’s test suggested no evidence of publication bias. Taken together, our results supported the notion that carriers of 677T or 677TT were at significantly increased risk of developing hypertension and HIP, but indicated caution in interpreting this result, because the study design made marginal significant contribution to the heterogeneity.

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References

  1. Staessen JA, Wang J, Bianchi G, Birkenhäger WH . Essential hypertension. Lancet 2003; 361: 1629–1641.

    Article  Google Scholar 

  2. Niu W, Wu S, Zhang Y, Li W, Ji K, Gao P et al. Validation of genetic association in apelin-AGTRL1 system with hypertension in a larger Han Chinese population. J Hypertens 2010; 28: 1854–1861.

    Article  CAS  Google Scholar 

  3. 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 

  4. Salanti G, Sanderson S, Higgins JP . Obstacles and opportunities in meta-analysis of genetic association studies. Genet Med 2005; 7: 13–20.

    Article  Google Scholar 

  5. Nakata Y, Katsuya T, Takami S, Sato N, Fu Y, Ishikawa K et al. Methylenetetrahydrofolate reductase gene polymorphism: relation to blood pressure and cerebrovascular disease. Am J Hypertens 1998; 11: 1019–1023.

    Article  CAS  Google Scholar 

  6. Nagy B, Hupuczi P, Papp Z . High frequency of methylenetetrahydrofolate reductase 677TT genotype in Hungarian HELLP syndrome patients determined by quantitative real-time PCR. J Hum Hypertens 2007; 21: 154–158.

    Article  CAS  Google Scholar 

  7. Kobashi G, Yamada H, Asano T, Nagano S, Hata A, Kishi R et al. Absence of association between a common mutation in the methylenetetrahydrofolate reductase gene and preeclampsia in Japanese women. Am J Med Genet 2000; 93: 122–125.

    Article  CAS  Google Scholar 

  8. Niu W, Qi Y, Hou S, Zhai X, Zhou W, Qiu C . Haplotype-based association of the renin-angiotensin-aldosterone system genes polymorphisms with essential hypertension among Han Chinese: the Fangshan study. J Hypertens 2009; 27: 1384–1391.

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  10. Ioannidis JP, Trikalinos TA . Early extreme contradictory estimates may appear in published research: the proteus phenomenon in molecular genetics research and randomized trials. J Clin Epidemiol 2005; 58: 543–549.

    Article  Google Scholar 

  11. Gao YY, Zhan SY, Yin XJ, Hu YH, Li LM . The relationship between methylenetetrahydrofolate reductase polymorphism and risk of essential hypertension. J Beijing Med Univ 1999; 31: 370–372 [in Chinese].

    CAS  Google Scholar 

  12. Wang L, Guo H, Li YM . MTHFR gene C677T polymorphism and variation of plasma homocysteine levels in primary hypertension. Tianjin Med J 2002; 30: 579–582 [in Chinese].

    CAS  Google Scholar 

  13. Sun XN, Li YM, Guo H . The gene polymorphisms of homocysteine metabolism enzymes and the associated factors in isolated systolic hypertension. Chin J Cardiol 2003; 31: 269–273 [in Chinese].

    Google Scholar 

  14. Li JW, Ye L, Liu J, Li XY . Study on homocysteine metabolism-related enzymes gene polymorphisms in elderly essential hypertension patients with peripheral arterial occlusive disease. Chin J Geriatr Care 2005; 24: 332–335 [in Chinese].

    Google Scholar 

  15. Li XJ, Huang W . The analysis of MTHFR gene polymorphism in patients with renal damage caused by hypertension and patients with renal parenchymal hypertension. J Capital Univ Med Sci 2006; 27: 497–500 [in Chinese].

    Google Scholar 

  16. Hu RL, Zhao SQ, Niu GM, Zhang CY, Hu RL, Wang ZG et al. The association between gene polymorphisms of N5,10-methylene tetrahydrofolate reductase (MTHFR) and Mongol nation patients with primary hypertension disease and hypertension complicating cerebrovascular disease. Stroke Nerv Dis 2007; 14: 13–15 [in Chinese].

    Google Scholar 

  17. Tang Y, Hui C, Wu XY, Luo JW . The C677T point mutation of N5,10-methylene tetrahydrofolate reductase (MTHFR) and essential hypertension. Mol Cardiol Chin 2007; 7: 205–207 [in Chinese].

    Google Scholar 

  18. Xing XR, Hua Q . Relationships between the polymorphism of methylenetetrahydrofolate reductase gene C677T and hypertension, cardiac structure and function. Med J Chin PLA 2007; 32: 741–744 [in Chinese].

    CAS  Google Scholar 

  19. Lin PT, Cheng CH, Wei JC, Huang YC . Low plasma pyridoxal 5′-phosphate concentration and MTHFR 677C—>T genotypes are associated with increased risk of hypertension. Int J Vitam Nutr Res 2008; 78: 33–40.

    Article  CAS  Google Scholar 

  20. Wei SQ, Zheng JH, Shi DW, Zou LH, Bi L . The relationship of MTHFR gene polymorphism with gestational hypertension and plasma homocysteine levels. Chin J Mod Med 2001; 11: 10–12 [in Chinese].

    Google Scholar 

  21. Fu F, Liu H, Liao DL, Xiong LN, He XJ, Zhang W et al. Investigation of the relationship between polymorphism of methylenetetrahydrofolate reductase and pregnancy induced hypertension syndrome. Jiangxi Med J 2003; 38: 401–403 [in Chinese].

    Google Scholar 

  22. Li KS, Wang BY, Chen LM, Mao DW . Detection of methylenetetrahydrofolate reductase gene polymorphism. Chin J Public Health 2004; 20: 762–764 [in Chinese].

    CAS  Google Scholar 

  23. Niu XM, Zhang XY . The relationship between plasma homocysteine metabolism and gestational hypertension. Chin J Obstet Gynecol 2004; 39: 347–348 [in Chinese].

    Google Scholar 

  24. Wang HY, Li CM, Wang Z, Yang F . Relationships between polymorphisms of angiotensin-converting enzyme and methylenetetrahydrofolate reductase genes and genetic susceptibility to pregnancy induced hypertension. Chin J Obstet Gynecol 2004; 39: 369–372 [in Chinese].

    CAS  Google Scholar 

  25. Tian G, She DX, Qi QH . Genetic research between gene polymorphisms of homcysteine metabolism-related enzymes and preeclampsia. Chin J Thromb Hemost 2005; 11: 197–199 [in Chinese].

    Article  Google Scholar 

  26. Wang SM, Shen R, Shi XY, Jiang T, Liu XM, Shi YL et al. The relationship between MTHFR gene polymorphism and gestational hypertension syndrome. Reprod Contracept 2006; 26: 378–379 [in Chinese].

    Google Scholar 

  27. Zhang ZH, Zhang RJ, Liu AM, Xu Q, Liu ZH . Study on eNOS gene and MTHFR gene polymorphisms in preeclampsia. Chin J Birth Health Hered 2007; 15: 21–24 [in Chinese].

    Google Scholar 

  28. Ding YS, Guan LX, Wang YH, Zhao L, Chen W . Study on MTHFR and eNOS gene polymorphisms in pregnancy-induced hypertension in the Hans of Weifang area. Chin J Birth Health Hered 2008; 16: 12–14 [in Chinese].

    CAS  Google Scholar 

  29. Wang SM, Wang LG, Liu XJ, Wu AH, Yu JC, Shi H . Investigation on the association between MTHFR gene C677T polymorphism and preeclampsia. Chin J Woman Child Health 2008; 23: 552–554 [in Chinese].

    Google Scholar 

  30. Shen XN, Huang YP, Tang SH, Zhang CL, Chen WS . The relationship between the polymorphism of MTHFR gene preeclampsia. J Pract Obstet Gynecol 2009; 25: 236–238 [in Chinese].

    Google Scholar 

  31. Kosmas IP, Tatsioni A, Ioannidis JP . Association of C677T polymorphism in the methylenetetrahydrofolate reductase gene with hypertension in pregnancy and pre-eclampsia: a meta-analysis. J Hypertens 2004; 22: 1655–1662.

    Article  CAS  Google Scholar 

  32. Qian X, Lu Z, Tan M, Liu H, Lu D . A meta-analysis of association between C677T polymorphism in the methylenetetrahydrofolate reductase gene and hypertension. Eur J Hum Genet 2007; 15: 1239–1245.

    Article  CAS  Google Scholar 

  33. Sohda S, Arinami T, Hamada H, Yamada N, Hamaguchi H, Kubo T . Methylenetetrahydrofolate reductase polymorphism and pre-eclampsia. J Med Genet 1997; 34: 525–526.

    Article  CAS  Google Scholar 

  34. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG . A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA 1995; 274: 1049–1057.

    Article  CAS  Google Scholar 

  35. Ruano-Ravina A, Pérez-Ríos M, Barros-Dios JM . Population-based versus hospital-based controls: are they comparable? Gac Sanit 2008; 22: 609–613.

    Article  Google Scholar 

  36. Yu K, Zhang J, Zhang J, Dou C, Gu S, Xie Y et al. Methionine synthase A2756G polymorphism and cancer risk: a meta-analysis. Eur J Hum Genet 2010; 18: 370–378.

    Article  CAS  Google Scholar 

  37. Pereira TV, Nunes AC, Rudnicki M, Yamada Y, Pereira AC, Krieger JE . Meta-analysis of the association of 4 angiotensinogen polymorphisms with essential hypertension: a role beyond M235T? Hypertension 2008; 51: 778–783.

    Article  Google Scholar 

  38. Jie L . Obstetrics and Gynecology. Beijing: People’s Medical Publishing House, (1996: 4th; 2000: 5th; 2004: 6th).

Download references

Acknowledgements

This work was supported by the SMC Excellent Young Faculty Award of Shanghai Jiao Tong University (WN), Seed Foundation of Development on Science and Technology by President of Capital Medical University Affiliated Beijing Anzhen Hospital (2010Z10), Shanghai ‘Chen Guang’ Project (09CG12), the Natural Science Foundation of Shanghai (09ZR1426200), and the National Science Foundation for Young Scientists of China (Grant Number: 30900808, 81000109).

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  1. W-Q Niu and Y-G You: These authors are joint first authors.

Authors and Affiliations

  1. Shanghai Key Laboratory of Vascular Biology and Department of Hypertension, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    W-Q Niu

  2. Laboratory of Vascular Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Shanghai, China

    W-Q Niu

  3. Shanghai Institute of Hypertension, Shanghai, China

    W-Q Niu

  4. Beijing Tropical Medicine Research Institute, Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China

    Y-G You

  5. Department of Epidemiology, Capital Medical University Affiliated Beijing Anzhen Hospital, Beijing Institute of Heart, Lung & Blood Vessel Diseases, Beijing, China

    Y Qi

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Correspondence to W-Q Niu or Y Qi.

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Niu, WQ., You, YG. & Qi, Y. Strong association of methylenetetrahydrofolate reductase gene C677T polymorphism with hypertension and hypertension-in-pregnancy in Chinese: a meta-analysis. J Hum Hypertens 26, 259–267 (2012). https://doi.org/10.1038/jhh.2011.11

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