title: Association between methionine synthase reductase A66G polymorphism and the risk of congenital heart defects: evidence from eight case-control studies.
abstract: Methionine synthase reductase (MTRR) plays a major role in hyperhomocysteinemia, a risk factor related to the occurrence of congenital heart defects (CHDs). However, the associations between MTRR polymorphism and CHDs have been inconclusive. Thus, a metaanalysis of eight case-control studies was conducted to investigate 3,592 cases and 3,638 control subjects for MTRR A66G polymorphism to identify the association. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were used to assess the strength of the association. The results showed that MTRR A66G polymorphism was associated with a higher CHD risk in the allele comparison (G vs A: OR 1.163; 95 % CI 1.016-1.330; P heterogeneity = 0.004), the homozygote comparison (GG vs AA: OR 1.332; 95 % CI 1.020-1.740; P heterogeneity = 0.035), and the dominant model (GG/AG vs AA: OR 1.218; 95 % CI 1.001-1.482; P heterogeneity = 0.001). In the subgroup analysis, this polymorphism was associated with CHDs in Asians in the homozygote comparison (GG vs AA: OR 1.427; 95 % CI 1.017-2.001; P heterogeneity = 0.019) and the allele comparison (G vs A: OR 1.203; 95 % CI 1.018-1.422; P heterogeneity = 0.002). In summary, the metaanalysis demonstrated that MTRR A66G polymorphism is a risk factor for CHDs. Further studies should be performed to investigate the association of plasma homocysteine levels, enzyme activity, parental genotypes, and vitamin complex intakes with the risk of CHDs.
authors.affiliation: Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, 210008, China.
authors.forename: Di
authors.initials: D
authors.lastname: Yu
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Shutong
authors.initials: S
authors.lastname: Shen
authors.forename: Changfeng
authors.initials: C
authors.lastname: Fan
authors.forename: Weiyan
authors.initials: W
authors.lastname: Zhang
authors.forename: Xuming
authors.initials: X
authors.lastname: Mo
mesh_terms: D016022:Case-Control Studies; D004247:DNA / Q000235:genetics*; D005287:Ferredoxin-NADP Reductase / Q000235:genetics* / Q000378:metabolism; D005420:Flavoproteins; D014943:Global Health; D006330:Heart Defects, Congenital / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015994:Incidence; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D005420:Flavoproteins; D004247:DNA; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase