铀矿工GSTP1基因多态与MGMT基因和p16基因甲基化的关系  

Glutathione S-transferase P1 polymorphism is associated with aberrant promoter methylation of O^6-methylguanine-DNA methyltransferase and p16 in uranium miners

作　　者：苏世标[1] 靳雅丽[1] 张卫[1] 杨鲁静[1] 聂继华[1] 童建[1] 

机构地区：[1]苏州大学放射医学与公共卫生学院卫生毒理学教研室,江苏苏州215007

出　　处：《中国职业医学》2006年第2期82-85,共4页China Occupational Medicine

基　　金：国家自然科学基金项目资助(30371226);江苏省重点实验室开放课题基金(KJS01068);放射医学重点学科(FY050211)

摘　　要：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。Objective To study the relationship between glutathione S-transferase P1 （GSTP1） polymorphisms and methyla- tion of O^6-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 lle/lle（42 eases）, genotype lle/Val（25 cases）, genotype Val/Val（3 eases） were 14.2% , 8.6% and 18.6%, respectively. Compared with genotype lle/lle, functional polymorphie variants of the GSTP1 associated with MGMT, p16 or MGMT promoter methylation in sputum were at high risk[ P = 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.

关 键 词：铀矿 氡及子体 谷胱甘肽S-转移酶P1 多态性 癌症 6-氧-甲基嘌呤-DNA甲基转移酶 p16 甲基化 职业暴露 

分 类 号：R730.231[医药卫生—肿瘤] R135[医药卫生—临床医学]