叶酸代谢相关酶系基因多态性与不良孕史的相关性研究

Correlation between gene polymorphisms of folate metabolism related enzymes and adverse pregnancy history

目的探讨亚甲基四氢叶酸还原酶(MTHFR)、甲硫氨酸合成酶还原酶(MTRR)、还原叶酸载体(RFC-1)及蛋氨酸合酶(MTR)等叶酸代谢酶系基因多态性与不良孕史的关系。方法收集2012年3月至2015年4月本院未孕女性213例,根据既往有无不良孕史分为不良孕史组65例(研究组)和无不良孕史组148例(对照组)。采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法检测MTHFR、MTRR、RFC-1及MTR基因分布频率,根据各基因位点功能、纯合、杂合出现频率将叶酸利用能力分为正常、略差、差、很差四个等级,比较基因多态性与不良孕史的关系及两组叶酸利用能力分布差异。结果携带MTHFR TT基因型的母亲既往不良孕史风险高于MTHFR CC+CT基因型(OR=3.235,95%CI:1.223~10.215,P<0.05),携带MTRR GG基因型的母亲既往不良孕史风险同样高于AA+AG基因型(OR=3.982,95%CI:1.631~9.990,P<0.05);而RFC-1 AA与AG+GG基因型、MTR GG与AA+AG基因型既往不良孕史风险比较,差异(P>0.05);研究组叶酸利用能力正常、略差率分别为1.54%、20.00%,低于对照组的33.78%和41.22%,而差和很差率分别为44.62%和33.85%,高于对照组的13.51%和1.49%(P<0.05)。结论母亲携带MTHFR 677C>T基因型、MTR66A>G基因型与不良孕史有关,而RFC-1 80G>A基因型,MTR 2756A>G基因型与不良孕史无显著相关性。

Objective To evaluate the correlation between folate metabolism enzymes gene polymorphism of methylenetetrahydrofolate reductase（MTHFR）, methionine synthase reductase（MTRR）, reduced folate carrier（RFC-1） and methionine synthase（MTR） and adverse pregnancy history. Methods From Mar 2012 to April 2015, 213 Peri-ceonceptional women in our hospital were divided into adverse pregnancy history（study group, n=65） and no adverse pregnancy history group（control group, n=148） based on past adverse pregnancy history. Gene frequency distributions of MTHFR, MTRR, RFC-1 and MTR were detected by polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP）. Absorption capacity of folic acid were divided into four grades（normal, slightly worse, poor, much poor） according to function of gene locus, homozygous and heterozygous frequency. Correlation of gene polymorphism and adverse pregnancy history was analyzed and folic acid absorbed capacity was compared. Results Risk of previous adverse pregnancy history of MTHFR TT genotype was higher than MTHFR CC＋CT genotype（OR=3.235, 95% CI： 1.223～10.215, P〈0.05）. Risk of MTRR GG genotype was higher than AA＋AG genotype as well（OR=3.982, 95% CI： 1.631～9.990, P〈0.05）. There was no significant risk difference between RFC-1 AA and AG＋GG genotype, MTR GG and AA ＋ AG genotype（P〈0.05）. The proportion of normal, slightly worse in folic acid absorption of study group（1.54% and 20.00%） were lower than control group（33.78% and 41.22%）, while poor, very poor ratio of study group（44.62% and 33.85%） were higher than control group（13.51% and 1.49%）（P〈0.05）. Conclusions MTHFR 677CT genotype and MTR 66AG genotype associated with adverse pregnancy history. Whereas no significant correlation between RFC-1 80GA genotype, MTR 2756AG genotype and adverse pregnancy history were found.