中国山西人群中叶酸代谢基因MTRR 和MTHFR 与复杂先天畸形关联研究

目的 探讨叶酸代谢基因蛋氨酸合成酶还原酶（MTRR）和5,10 甲基四氢叶酸还原酶（MTHFR）基因多态性是否与复杂先天畸形相关，进一步研究其是否与三胚层发育来源的复杂先天畸形相关。方法 选取中国山西省250 例出生缺陷病例（包括先心病、神经管畸形和颅面畸形等复杂先天畸形）为研究对象，选择MTRR 单核苷酸多态性位点 rs1801394 和MTHFR 单核苷酸多态性位点rs1801133，利用SNaPshot 方法进行基因分型，并与420 例正常对照人群进行比较。结果 rs1801394 和 rs1801133 分别与多个先天出生缺陷有关。在隐性模型下，rs1801394 GG 基因型和rs1801133 CC 基因型的个体发生先天缺陷的概率低, 为出生缺陷的保护性因素。rs1801133 隐性纯合作为保护性因素与外胚层和内胚层器官来源复杂先天畸形相关，rs1801394 隐性纯合作为保护性因素与外胚层、中胚层和内胚层器官来源的复杂先天畸形相关。结论 中国山西人群中叶酸代谢基因MTRR 和MTHFR 与复杂先天畸形相关，并与胚层发育相关。

Association of folate metabolism genes MTRR and MTHFR with complex congenital abnormalities among Chinese population in Shanxi Province, China

Objective To explore the association of polymorphisms in folate metabolism genes, methionine synthase reductase (MTRR) gene and 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, with complex congenital abnormalities and to further investigate its association with complex congenital abnormalities derived from three germ layers. Methods A total of 250 cases of birth defects (with complex congenital abnormalities including congenital heart disease, neural tube defects, and craniofacial anomalies) in Shanxi Province, China were included in the study. MTRR single nucleotide polymorphism (SNP) (rs1801394) and MTHFR SNP (rs1801133) were genotyped by the SNaPshot method, and the genotyping results were compared with those of controls (n=420). Results SNPs rs1801394 and rs1801133 were associated with multiple birth defects. For the recessive model, individuals with GG genotype at rs1801394 and CC genotype at rs1801133 had a relatively low risk of developing birth defects, so the two genotypes were protective factors against birth defects. The homozygous recessive genotype at rs1801133, which served as a protective factor, was associated with ectoderm- or endoderm-derived complex congenital abnormalities, while the homozygous recessive genotype at rs1801394, which served as a protective factor, was associated with ectoderm-, mesoderm- or endoderm-derived complex congenital abnormalities. Conclusions Among the Chinese population in Shanxi Province, the SNPs in folate metabolism genes (MTRR and MTHFR) are associated with complex congenital abnormalities and related to ectoderm, mesoderm or endoderm development.