叶酸代谢相关基因的多态性对学龄前儿童神经心理发育的影响

Impact of Gene Polymorphisms Associated with Folate Metabolism on Neuropsychological Development of Preschool Children

目的:研究亚甲基四氢叶酸还原酶(MTHFR)、甲硫氨酸合成酶还原酶(MTRR)和甲硫氨酸合成酶(MTR)等叶酸代谢通路中关键酶的单核苷酸多态性(SNP)对汉族学龄前儿童神经心理发育的影响。方法:选取来自贵定县和嵩县的318名汉族学龄前儿童为研究对象,采用KASP SNP分型技术对MTHFR A1298C/C677T、MTRR A66G、MTR A2756G 4个位点进行基因分型,分析4个SNPs对发育商(DQ)和智力指数(MI)的影响。结果:MTHFR C677T位点不同基因型组的DQ和MI均存在显著性差异(P<0.05),MTHFR A1298C位点不同基因型只有DQ存在显著性差异(P<0.01)。MTRR A66G和MTR A2756G位点不同基因型的DQ和MI均无显著性差异(P>0.05)。根据MTHFR A1298C和MTHFR C677T风险基因的A和T的携带,采用风险基因累积效应分析结果显示,携带不同数量风险基因型的DQ差异有统计学意义(P<0.01)。结论:MTHFR 1298CC纯合突变型对神经心理发育有保护作用,而MTHFR C677T位点的T突变会增加儿童患神经心理发育障碍性疾病的风险。MTRR A66G和MTR A2756G位点与儿童的神经心理发育无关。

【Objective】To investigate the impact of single nucleotide polymorphisms(SNPs)in key enzymes of the folate metabolic pathway,including methylenetetrahydrofolate reductase(MTHFR),methionine synthase reductase(MTRR)and methionine synthase(MTR),on neuropsychological development in Han preschool children.【Method】A total of 318 Han Chinese pre-school children from Guiding and Song counties were recruited to genotype the four loci MTHFR(A1298C/C677T),MTRR(A66G)and MTR(A2756G)using KASP SNP typing technology to investigate the impact of these four SNPs on DQ and MI.【Result】The study revealed that the disparities in DQ and MI among genotype groups at the MTHFR C677T locus were statistically significantly different(P<0.05).The disparity in DQ among the diverse genotype groups at the MTHFR A1298C locus exhibited statistical significance(P<0.01).Conversely,there were no statistically significant variances in DQ and MI between genotype groups at MTRR A66G and MTR A2756G loci(P>0.05).Defining MTHFR 1298AA/CC and MTHFR 677CT/TT as genotypes carrying risk,a statistically significant difference in DQ was observed between groups with varying numbers of risk genotypes(P<0.01).【Conclusion】The MTHFR 1298CC pure mutant type is protective against neuropsychological development,and the T mutation in the MTHFR C677T locus increases the risk of neuropsychological disorders in children.The MTRR A66G and MTR A2756G loci are not associated with neuropsychological development in preschool children.