南京地区汉族女性叶酸代谢关键酶基因多态性分布情况

Distributions of gene polymorphisms of key enzymes of folic acid metabolism in Han women in Nanjing region

目的 针对南京地区汉族女性开展分子流行病学调查,研究叶酸代谢关键酶5, 10-亚甲基四氢叶酸还原酶(MTHFR)和甲硫氨酸合成酶还原酶(MTRR)的基因多态性分布。方法 选取2018年7月—2020年6月到南京市红十字医院进行孕期检查的汉族健康女性476例为研究对象,采集所有研究对象口腔黏膜上皮脱落细胞,抽提基因组DNA,使用荧光定量PCR方法检测MTHFR C677T、A1298C及MTRR A66G基因多态性,并进行统计分析。结果 入组对象的MTHFR C677T、A1298C及MTRR A66G基因多态性分布符合遗传平衡,差异均无统计学意义(均P>0.05)。汉族女性MTHFR 677 CC、CT及TT的基因型频率分别为26.7%、47.9%及25.4%,C、T等位基因频率分别为50.6%、49.4%;MTHFR 1298 AA、AC及CC的基因型频率分别为66.4%、30.5%及3.15%,A、C等位基因频率分别为81.6%、18.4%;MTRR 66 AA、AG及GG的基因型频率分别为56.1%、39.1%及4.83%,A、G等位基因频率分别为75.6%、24.4%。汉族女性MTHFR C677T和A1298C两位点连锁有6种组合,频率最高的是CT/AA(32.1%),没有CT/CC、TT/AC及TT/CC组合。两位点间存在连锁不平衡(D’=1.0,r^(2)=0.22)。结论 获取南京地区汉族女性MTHFR和MTRR基因多态性的群体遗传学特征,其中关键基因位点MTHFR C677T的高风险TT基因型比例为25.4%,低于已有报道的山东省淄博市、河南省新乡市及辽宁省沈阳市等地数据,高于浙江省丽水市、广东省佛山市等地数据,说明叶酸利用能力中等,对于高风险人群还需加强孕期管理,为当地人群进行个体化增补叶酸提供理论依据。

Objective To conduct molecular epidemiological investigation among Han women in Nanjing region, research the distributions of gene polymorphisms of key enzymes of folic acid metabolism--5, 10-methylenetetrahydrofolate reductase(MTHFR) and methionine synthase reductase(MTRR). Methods From July 2018 to June 2020, 476 healthy Han women receiving prenatal examination in Nanjing Red Cross Hospital were selected as study object, exfoliated cells of oral mucosa were collected, genome DNA was extracted, fluorogenic quantitative PCR was used to detect gene polymorphisms of MTHFR C677 T, A1298 C, and MTRR A66 G, statistical analysis was performed. Results The distributions of gene polymorphisms of MTHFR C677 T, A1298 C, and MTRR A66 G conformed to Hardy-Weinberg equilibrium, there was no statistically significant difference(P>0.05). The frequencies of MTHFR 677 CC, CT, and TT genotypes in Han women were 26.7%, 47.9%, and 25.4%, respectively, the frequencies of C and T alleles were 50.6% and 49.4%, respectively. The frequencies of MTHFR 1298 AA, AC, and CC genotypes in Han women were 66.4%, 30.5%, and 3.15%, respectively, the frequencies of A and C alleles were 81.6% and 18.4%, respectively. The frequencies of MTRR 66 AA, AG, and GG genotypes in Han women were 56.1%, 39.1%, and 4.83%, respectively, the frequencies of A and G alleles were 75.6% and 24.4%, respectively. There were six combinations of MTHFR C677 T and A1298 C in Han women, the frequency of CT/AA was the highest(32.1%), CT/CC, TT/AC, and TT/CC combinations were not observed. There was linkage disequilibrium between the two loci(D’=1.0, r^(2)=0.22). Conclusion This study obtain the population genetic characteristics of MTHFR and MTRR gene polymorphisms in Han women in Nanjing region, the proportion of high-risk TT genotype of MTHFR C677 T locus is 25.4%, which is lower than those reported in Zibo City of Shandong Province, Xinxiang City of He’nan Province, and Shenyang City of Liaoning Province and higher than those reported in Lishui City of Zhejiang Province and Foshan City of Guangdong Province, which indicates that the utilization ability of folic acid in Han women in Nanjing region is moderate, management during pregnancy should be enhanced among the high-risk population, this study provide a theoretical basis for individual supplementation of folic acid among local population.