Association of methylenetetrahydrofolate reductase gene C677T polymorphism with polycystic ovary syndrome risk: a systematic review and meta-analysis update

• Published in: European journal of obstetrics & gynecology and reproductive biology Vol. 172; pp. 56 - 61
• Main Authors: Fu, Li-yuan, Dai, Li-meng, Li, Xiao-gang, Zhang, Kun, Bai, Yun
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.01.2014
• Subjects: Asian Continental Ancestry Group - genetics; European Continental Ancestry Group - genetics; Female; Genetic Predisposition to Disease; Humans; Meta-analysis; Methylenetetrahydrofolate reductase; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Obstetrics and Gynecology; Odds Ratio; Polycystic ovary syndrome; Polycystic Ovary Syndrome - genetics; Polymorphism; Polymorphism, Genetic; methylenetetrahydrofolate reductase; PCOS; OR; Hardy–Weinberg equilibrium; CI; HWE; MTHFR; confidence interval; odds ratio; polycystic ovary syndrome; Polymorphism; Meta-analysis; Polycystic ovary syndrome; Methylenetetrahydrofolate reductase
• ISSN: 0301-2115; 1872-7654
• DOI: 10.1016/j.ejogrb.2013.10.001

Abstract Objectives To re-estimate the association between methylenetetrahydrofolate reductase gene ( MTHFR ) C677T polymorphism and polycystic ovary syndrome (PCOS) risk by critically reviewing, analyzing and updating the current evidence. MTHFR C677T polymorphism has been studied as a possible risk factor for a variety of common conditions including heart disease, stroke and hypertension. Its association with PCOS was negative in a previous meta-analysis which had possible shortcomings. More studies have now been done but their results remain inconclusive. Study design Available case-control studies containing genotype frequencies of MTHFR C677T were chosen, and odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the association. Statistical analyses were performed using software Review Manager (Version 5. 2) and Stata (Version 11.0). Results Nine case-control studies including 638 PCOS and 759 healthy controls were identified. Meta-analysis showed a significant effect in the dominant model (TT+CT vs. CC: OR = 1.65, 95%CI = 1.28–2.12, P < 0.0001) and heterozygote comparison (CT vs. CC: OR = 1.83, 95%CI = 1.17–2.87, P = 0.008). In subgroup analysis stratified by ethnicity, MTHFR C677T variant was statistically significantly relevant to PCOS risk in European populations (TT+CT vs. CC: OR = 2.16, 95%CI = 1.50–3.12, P < 0.0001; CT vs. CC: OR = 2.11, 95%CI = 1.15–3.87, P = 0.02) but not in Asian populations (TT+CT vs. CC: OR = 1.29, 95%CI = 0.91–1.82, P = 0.15; CT vs. CC: OR = 1.31, 95%CI = 0.91–1.90, P = 0.15). Conclusions This meta-analysis indicates that the 677T allele increases PCOS susceptibility, and this relevance seems to be more intense in Europeans than in Asians.