Department of Cardiovascular Medicine, Second Affiliated Hospital of Nanchang University, No. 1 Min De Road, Nanchang, Jiangxi, China.
DNA Cell Biol. 2012 Feb;31(2):238-49. doi: 10.1089/dna.2011.1281. Epub 2011 Jul 22.
Many epidemiological studies have explored the relationships between three genetic polymorphisms of genes encoding homocysteine-metabolizing enzymes (methionine synthase [MTR] A2756G, methionine synthase reductase [MTRR] A66G, and N(5),N(10)-methylenetetrahydrofolate reductase [MTHFR] A1298C) and risk of coronary heart disease (CHD), but no conclusive results were obtained. Therefore, we performed a meta-analysis of 23 case-control studies. Odds ratio (OR) and 95% confidence interval (95% CI) were used to examine the strength of the associations. Among those primary studies, 22 studies were for Europeans, and one study focused on the MTR A2756G polymorphism in Asians. The results of combined analyses of the MTR A2756G polymorphism suggested that the G allele was associated with increased risk of CHD and myocardial infarction (MI) especially for Europeans (GG vs. AA for CHD: OR [95% CI]=1.63 [1.18-2.25], p(z)(-test)=0.001, p(heterogeneity)=0.274; GG+AG vs. AA for MI: OR [95% CI]=1.44 [1.08-1.93], p(z)(-test)=0.014, p(heterogeneity)=0.611). In addition, the G allele was also associated with higher risk CHD based on population-based case-control studies (PCC) (GG vs. AA: OR [95% CI]=1.75 [1.24-2.49], p(z)(-test)=0.002, p(heterogeneity)=0.316). The results suggested that the MTRR A66G polymorphism was not associated with risk of CHD for Europeans (AA vs. GG: OR [95% CI]=1.07 [0.59-1.94], p(z)(-test)=0.831, p(heterogeneity)<0.01). The results suggested that the C allele of the MTHFR A1298C polymorphism might be associated with the increased risk of MI for Europeans (CC vs. CA+AA: OR [95% CI]=1.37 [1.03-1.84], p(z)(-test)=0.033, p(heterogeneity)=0.668). However, when subgroup analyses for sources of controls were performed, conflicting results were obtained. The results suggested that the C allele was associated with decreased risk of CHD based on hospital-based case-control studies, but associated with increased risk of CHD based on PCC. This meta-analysis suggests that MTR A2756G polymorphism, but not MTRR A66G and MTHFR A1298C, is associated with risk of CHD for Europeans. Because of limitations and potential bias, more well-designed studies with larger sample size, especially focused on Asians and Africans, should be performed in the future.
许多流行病学研究探讨了编码同型半胱氨酸代谢酶的基因（蛋氨酸合成酶[MTR] A2756G、蛋氨酸合成酶还原酶[MTRR] A66G 和 N（5），N（10）-亚甲基四氢叶酸还原酶[MTHFR] A1298C）三个遗传多态性与冠心病（CHD）风险之间的关系，但未得出明确的结论。因此，我们对 23 项病例对照研究进行了荟萃分析。比值比（OR）和 95%置信区间（95%CI）用于检验关联的强度。在这些初步研究中，22 项研究针对欧洲人，一项研究专门针对亚洲人中的 MTR A2756G 多态性。MTR A2756G 多态性联合分析的结果表明，G 等位基因与 CHD 和心肌梗死（MI）风险增加有关，尤其是在欧洲人中（GG 与 AA 相比，CHD：OR[95%CI]=1.63[1.18-2.25]，p(z)(-test)=0.001，p(异质性)=0.274；GG+AG 与 AA 相比，MI：OR[95%CI]=1.44[1.08-1.93]，p(z)(-test)=0.014，p(异质性)=0.611）。此外，基于基于人群的病例对照研究（PCC），G 等位基因也与 CHD 风险增加相关（GG 与 AA：OR[95%CI]=1.75[1.24-2.49]，p(z)(-test)=0.002，p(异质性)=0.316）。结果表明，MTRR A66G 多态性与欧洲人 CHD 风险无关（AA 与 GG：OR[95%CI]=1.07[0.59-1.94]，p(z)(-test)=0.831，p(异质性)<0.01）。结果表明，MTHFR A1298C 多态性的 C 等位基因可能与欧洲人 MI 风险增加有关（CC 与 CA+AA：OR[95%CI]=1.37[1.03-1.84]，p(z)(-test)=0.033，p(异质性)=0.668）。然而，当进行对照来源的亚组分析时，得到了相互矛盾的结果。结果表明，C 等位基因与基于医院的病例对照研究的 CHD 风险降低有关，但与 PCC 中的 CHD 风险增加有关。这项荟萃分析表明，MTR A2756G 多态性，而不是 MTRR A66G 和 MTHFR A1298C，与欧洲人 CHD 风险有关。由于存在局限性和潜在的偏倚，未来应进行更多设计良好、样本量更大的研究，尤其是针对亚洲人和非洲人。
