DNA 甲基化转移酶1基因多态性与铅中毒易感性分析

Analysis on DNA methyltransferase 1 gene polymorphisms and susceptibility to lead poisoning

目的：探讨DNA甲基化转移酶1（DNMT1）基因多态性与铅中毒易感性的关系。方法采用病例-对照研究方法，以78例职业性慢性铅中毒患者为铅中毒组，以同企业、同工种及年龄相近的78名未发生铅中毒的铅作业工人为对照组。采集2组人群清晨空腹肘静脉血，采用多重聚合酶链式反应-连接酶检测反应分型法检测DNMT1 rs2228611及rs10854076位点单核苷酸多态性（ SNP）。结果2组人群DNMT1 rs2228611及rs10854076位点等位基因频率分布均符合遗传学Hardy-Weinberg平衡定律（ P＞0.05）。2组人群rs2228611位点3种基因型AA、AG、GG总体分布不同（P＜0.05），等位基因A、G的基因频率分布不同（P＜0.05），纯合子AA基因型携带者铅中毒易感性增高[比值比为7.88，95％可信区间为（1.56～39.84），P＜0.05]。2组人群rs10854076位点3种基因型CC、CG、GG总体分布及等位基因C、G的基因频率分布分别比较，差异均无统计学意义（ P＞0.05）；该位点不同基因型与铅中毒易感性无关（P＞0.05）。结论 DNMT1 rs2228611位点SNP与铅中毒易感性相关，纯合子AA基因型为风险基因型，可增加铅中毒的易感性。

Objective To explore the correlation between genetic polymorphisms of DNA methyltransferase 1 （ DNMT1 ） and susceptibility to lead poisoning .Methods A case-control study was performed among 78 patients diagnosed as occu-pational chronic lead poisoning （ lead poisoning group ） and 78 workers similarly exposed to lead but without poisoning man-ifestations （ control group ） , all the patients and the controls who were similar in work and age were chosen from the lead -acid battery factories in Guangzhou .The peripheral venous blood of two groups was collected , and then rs2228611 and rs10854076, two single nucleotide polymorphism （ SNP） in DNMT1 gene were detected by multiplex polymerase chain reaction-ligase detection reaction.Results The two SNP （rs2228611 and rs10854076） were in accordance with Hardy-Weinberg equilibrium （ P ＆gt;0.05 ） .There was significant difference in total distribution of AA , AG and GG genotype frequency of DNMT1 rs2228611 locus between the lead poisoning group and the control group （P＆lt;0.05）, and there was significant difference in A and G allelic frequencies between the two groups （P＆lt;0.05）.It showed that individual homozy-gous AA carriers for DNMT1 rs22286111 allele were much susceptible to lead poisoning （ Odds ratio：7.88, 95% confi-dence interval：1.56-39.84, P＆lt;0.05 ） .No significant difference was shown between lead poisoning group and control group on total distribution of CC , CG and GG genotype frequency （P＆gt;0.05）, and C and G allelic frequency of DNMT1 rs10854076 locus （P＆gt;0.05）.The genotype of rs10854076 might not contribute to the genetic susceptibility of lead poi-soning （P＆gt;0.05）.Conclusion The genetic polymorphism of DNMT1 rs2228611 is associated with the susceptibility of lead poisoning .The DNMT1 rs2228611 AA genotype is a potential susceptible factor for lead poisoning .