4063例叶酸代谢关键酶基因多态性特点及其与同型半胱氨酸的相关性

The Study on Polymorphisms of Key Enzyme Genes of Folate Metabolism and Their Correlation with Homocysteine in 4063 Cases

目的探讨备孕夫妇叶酸代谢酶基因多态性分布特征及其与同型半胱氨酸(Hcy)的关系,为指导个体化叶酸增补方案提供理论依据。方法随机抽取2020年7月至2022年6月符合生育政策并计划怀孕的夫妇基本资料及外周血,最终4063例纳入研究,采集其外周血测定5,10-亚甲基四氢叶酸还原酶(MTHFR)rs1801133、rs1801131位点和甲硫氨酸合成酶还原酶(MTRR)rs1801394位点的基因型及血清Hcy水平,进一步展开分析。结果本研究受检人群叶酸代谢酶基因多态性分布符合HW遗传平衡,其中MTHFR rs1801133和rs1801131位点存在连锁不平衡(D’=0.98,r2=0.14)。MTHFR基因rs1801133位点的CC、CT及TT基因型频率分别为42.31%、44.47%和13.22%;MTHFR基因rs1801131位点的AA、AC及CC基因型频率分别为62.15%、33.20%和4.65%;MTRR基因rs1801394的AA、AG及GG基因型频率分别为55.06%、38.59%和6.35%。不同叶酸代谢酶基因型/叶酸代谢障碍风险人群之间Hcy水平差异无统计学意义(P>0.05);男性在相同叶酸代谢酶基因型/叶酸代谢障碍风险下Hcy水平更高(P<0.001);35岁以下MTHFR rs1801133位点CC基因型、rs1801131位点AC和CC基因型的人群Hcy水平更高(P<0.05)。结论桃源县叶酸代谢酶基因多态性分布具有自身特点,未来需要结合遗传因素和环境因素格外关注备孕期男性及非高龄人群(<35岁)并进行叶酸补充指导和监测,这可能成为进一步降低新生儿出生缺陷的重要途径。

Objective To explore the polymorphism of folate metabolizing enzyme gene and its relationship with homocysteine(Hcy)in couples in Taoyuan County,Hunan Province,in order to provide theoretical basis for individualized folic acid supplementation in this area.Methods We collected the basic information of 4063 subjects in Taoyuan County Maternal and Child Health Hospital from July 2020 to June 2022.The genotypes of of sites rs1801133 and rs1801131 of 5,10-methylenetetrahydrofolate reductase(MTHFR)and rs1801394 of methionine synthase reductase(MTRR)and blood Hcy levels in peripheral blood were collected for further analysis.Results The distribution of folate metabolizing enzyme gene polymorphisms in the tested population was consistent with Hardy-Weinberg genetic balance.MTHFR rs1801133 and rs1801131 had linkage disequilibrium(D'=0.98,r2=0.14).The frequency of CC,CT and TT genotype of MTHFR rs1801133 gene was 42.31%,44.47%and 13.22%.The frequency of AA,AC and CC genotype of MTHFR rs1801131 gene site was 62.15%,33.20%and 4.65%respectively.The frequency of AA,AG and GG genotype of MTRR rs1801394 gene site was 55.06%,38.59%and 6.35%respectively.There was no difference in Hcy level between different folate metabolism genotypes and among people at different risk of folate metabolism disorder(P>0.05),but the Hcy level in men with the same folate metabolism genotype or folate metabolism disorder risk was significantly higher(P<0.001).The Hcy level of under 35 years old was higher in MTHFR rs1801133 CC genotype,rs1801131 AC and CC genotype(P<0.05).Conclusion The distribution of folic acid metabolic enzyme gene polymorphisms in this region has its own characteristics.In the future,it is necessary to pay special attention to pre-pregnancy men and young people(<35 years old)in combination with genetic factors and environmental factors,and conduct folic acid supplementation guidance and monitoring,which may become an important way to further reduce newborn birth defects.