铀矿工GSTP1基因多态与MGMT基因和p16基因甲基化的关系

目的探讨氡职业暴露人群谷胱甘肽S-转移酶P1(GSTP1)基因多态与痰细胞6-氧-甲基嘌呤-DNA甲基转移酶(MGMT)和p16基因甲基化的关系。方法用聚合酶链反应-限制性片段长度多态性法(PCR-RFLP)确定70例氡职业暴露人群GSTP1的基因型;用聚合酶链反应-甲基化特异性法(MSP)确定痰细胞中MGMT和p16基因的甲基化与非甲基化状态。结果在70名铀矿工中,GSTP1基因A105G位点的纯合子(Ile/Ile)42例,杂合子(Ile/Val)25例和纯合子(Val/Val)3例。MGMT、p16基因甲基化率和总甲基化率分别为14.2%、8.6%和18.6%。与携带Ile/Ile人群相比,携带异常等位基因(Ile/Val与Val/Val)的人群MGMT基因甲基化和总甲基化率增加P=0.037,OR=4.8,95%CI(1.1~21.0);P=0.016,OR=5.1,95%CI(1.4~19.6)];p16基因甲基化率差异无统计学意义P=0.057,OR=4.6,95%CI(0.8~29.2)]。结论GSTP1(A105G)基因多态性与氡致MGMT基因甲基化和总甲基化的易感性有关。

Glutathione S-transferase P1 polymorphism is associated with aberrant promoter methylation of O6-methylguanine-DNA methyltransferase and p16 in uranium miners

Objective To study the relationship between glutathione S-transferase P1 (GSTP1) polymorphisms and methylation of O6-methylguanine-DNA methyltransferase and p16 gene in sputum of uranium miners. Methods 70 uranium miners were selected to determine GSTP1(A105G) genotypes using PCR-RFLP and to define MGMT and p16 gene methylation by MSP. Results The rates of MGMT, p16 gene methylation and p16 or MGMT methylation in sputum of uranium miners with GSTP1 (A105G) genotype Ile/Ile(42 cases), genotype Ile/Val(25 cases), genotype Val/Val(3 cases) were 14.2% , 8.6% and 18.6%, respectively. Compared with genotype Ile/Ile, functional polymorphic variants of the GSTP1 associated with MGMT, p16 or MGMT promoter methylation in sputum were at high riskP=0.037, OR=4.8,95%CI(1.1-21.0); P=0.009,OR=5.1,95%CI(1.4-19.6)];there was no significant difference between the rates of p16 P=0.057, OR=4.6,95%CI(0.8-29.2)]. Conclusion Functional polymorphic variants of the GSTP1 were associated with MGMT promoter methylation in sputum of uranium miners.