Congenital heart defects and genetic variants in the methylenetetrahydroflate reductase gene
Congenital heart defects and genetic variants in the methylenetetrahydroflate reductase gene
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DOI：
10.1136/jmg.2005.032656
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发表时间：
2006-02-01
影响因子：
4
通讯作者：
Cleves, MA
中科院分区：
文献类型：
--
作者：
Hobbs, CA;James, SJ;Cleves, MA
背景：大多数非综合征性先天性心脏病 (CHD) 是由母亲生活方式因素、环境暴露以及母亲和胎儿遗传变异之间复杂的相互作用引起的。据报道，母亲围孕期摄入含叶酸的维生素补充剂可降低冠心病的风险。亚甲基四氢叶酸还原酶(MTHFR)基因677C-->T和1298A-->C多态性降低酶活性。目的：探讨CHD与母胎MTHFR多态性的关系。方法：对375个核心家庭进行研究。传输/不平衡测试用于测试完整三元组中的传输失真。采用对数线性方法来测试先心病与母体和后代多态性之间的关联，并独立估计母体和胎儿变异对相对风险的贡献。估计了单倍型频率并进行了单倍型传递不平衡测试。结果：1298C 等位基因的传递频率低于预期 (p = 0.0013)。 677T等位基因的传递没有扭曲，也没有任何单核苷酸多态性的传递中存在亲本效应的证据。 677C - 1298C 单倍型的传播频率也低于预期 (p = 0.0020)。遗传 1 个 1298C 等位基因拷贝的相对风险为 0.64（95% 置信区间，0.48 至 0.87），遗传 2 个 1298C 等位基因拷贝的相对风险为 0.38（0.21 至 0.70）。结论：MTHFR 1298C 等位基因对 CHD 的明显保护作用可能有多种解释，需要进一步研究。
Background: Most non-syndromic congenital heart defects (CHD) are caused by a complex interaction between maternal lifestyle factors, environmental exposures, and maternal and fetal genetic variants. Maternal periconceptional intake of folic acid containing vitamin supplements is reported to decrease the risk of CHD. The 677C-->T and 1298A-->C polymorphisms in the methylenetetrahydrofolate reductase ( MTHFR) gene decrease enzyme activity.Objective: To examine the relation between CHD and maternal and fetal MTHFR polymorphismsMethods: 375 nuclear families were studied. The transmission/ disequilibrium test was used to test for transmission distortion in complete triads. A log-linear approach was used to test for associations between CHD and maternal and offspring polymorphisms, and to estimate independently the contributions of maternal and fetal variants to relative risks. Haplotype frequencies were estimated and a haplotype transmission disequilibrium test carried out.Results: The 1298C allele was transmitted less often than expected ( p = 0.0013). There was no distortion in the transmission of the 677T allele, neither was there evidence of a parent of origin effect in the transmission of either of the single nucleotide polymorphisms. The 677C - 1298C haplotype was also transmitted less often than expected ( p = 0.0020). The relative risk associated with inheriting one copy of the 1298C allele was 0.64 (95% confidence interval, 0.48 to 0.87) and the that associated with inheriting two copies of the 1298C allele, 0.38 (0.21 to 0.70).Conclusions: The apparent protective effect of the MTHFR 1298C allele against CHD could have several explanations and further study is needed.