摘要目的 探讨砷代谢相关酶三价砷甲基转移酶[arsenic(+3 oxidation state)methyltranaferase,AS3MT]单核苷酸多态性与地方性砷中毒患病风险的关系.方法 采用聚合酶链反应-限制性酶切片段多态性-单链构象多态性(PCR-RFLP-SSCP)技术对79名砷中毒患者和110名正常健康人群外周血中AS3MT基因第8内含子和第9外显子的突变情况进行初筛,并进一步对异常带型进行直接DNA测序,以确定突变位点及类型.对AS3MT基因多态性进行单因素分析和多因素非条件Logistic回归分析.结果 病例组AS3MT基因第8内含子上9149位碱基(AS3MT-9149)A→C突变的发生率(19.0％,15/79)低于对照组(23.6％,26/110),病例组AS3MT基因第9外显子上287位密码子(AS3MT-287)ATG→AC/TG突变的发生率(10.1％,8/79)低于对照组(11.8％,13/110),但差异均无统计学意义(P均＞0.05).在多因素分析中调整年龄、性别等因素后,AS3MT基因多态性与地方性砷中毒发病仍无统计学意义[AS3MT-9149:比值比(OR)=0.59,95％可信区间(CI)为0.26～1.31,P=0.195；AS3MT-287:OR=0.85,95％CI为0.32 ～ 2.30,P=0.751].结论 AS3MT-9149和AS3MT-287多态性与地方性砷中毒易感性无显著关系,出现这种情况的原因可能与分析的样本量较小,或者是有关的多态性位点在AS3MT基因其他的外显子或非编码区上有关.

abstractsObjective To investigate the association between arsenic(+3 oxidation state) methyltransferase (AS3MT) genetic polymorphism and susceptibility to endemic arsenism.Methods Polymerase chain reactionrestriction fragment length polymorphism-single strand conformation polymorphism(PCR-RFLP-SSCP) technology was performed to detect mutations of AS3MT gene intron 8 and exon 9 in genome DNA of the 79 cases and 110 controls.PCR products with abnormal band forms were further sequenced to find the types and sites of mutation.Chi-square test and multivariate Logistic analyses were conducted.Results The incidence of the 9149 base mutation(A→C) in AS3MT gene intron 8(AS3MT-9149) in case group(19.0％,15/79) was lower than that in control group (23.6％,26/110).The incidence of the codon 287 mutation(ATG→AT/CG) in AS3MT gene exon 9(AS3MT-287)in case group(10.1％,8/79) was lower than that in control group (11.8％,13/110).However,statistical analysis indicated no significant difference in both mutations between two groups[AS3MT-9149:odds ratio(OR) =0.59,95％ confidence interval(CI):0.26-1.31,P =0.195; AS3MT-287:OR =0.85,95％ CI:0.32-230,P =0.751].Conclusions There are no significant association between the genetic polymorphisms of AS3MT-9149,AS3MT-287 and the susceptibility to endemic arsenism.Similarly,due to small sample amount,we can not exclude the possibility that these gene polymorphisms are related to susceptibility to endemic arsenism.