摘要目的 探讨多药耐药相关蛋白1和2(MRP1、MRP2)基因突变对地方性砷中毒患者表型的影响.方法 在山西省饮水型地方性砷中毒高发区朔州市朔城区的3个自然村.对常住人口采用单纯随机抽样法抽样并进行问卷调查,从问卷中筛选出在当地居住20年以上的居民作为调查对象并进行临床检查.依据<地方性砷中毒诊断标准)(WS/T 211-2001),将临床诊断为地方性砷中毒的75名患者作为砷中毒组,其余164人作为对照组.采集两组人群外周血,其中砷中毒组75份,对照组118份,提取DNA.对MRP1基因第2、17、23外显子和MRP2基因第10、18、31外显子进行扩增,采用聚合酶链反应-单链构象多态性(PCR-SSCP)方法检测目的 基凶的突变情况,并应用多元Logistic回归模型比较基因突变率在砷中毒组和对照组间的差异.结果 共收回有效问卷239份,其中砷中毒组75份,对照组164份.两组人群在年龄[(58.85±11.26)岁与(45.73±11.92)岁]、性别[男性57.3%(43/75)与27.4%(45/164)]、吸烟[46.7%(35/75)与21.3%(35/164)]、农药接触史[41.3%(31/75)与29.3%(48/164)]比较,差异有统计学意义[比值比(OR)分别为3.378、3.553、3.225、1.864,P＜0.01或＜0.05];在饮酒[17.3%(13/75)与8.5%(14/164)]、果蔬摄入[5.3%(4/75)与9.1%(15/164)]、肉蛋奶摄人[34.7%(26/75)与30.5%(50/164)]比较,差异无统计学意义(OR值分别为1.836、0.560、1.210,P＞0.05).MRP1的第23外显子和MRP2的第18外显子在砷中毒组和对照组中均未检测到突变:MRP1的第2外显子在砷中毒组和对照组中突变检出率分别为8.00%(6/75)和5.93%(7/118),第17外显子突变检出率分别为13_33%(10/75)和8.47%(10/118);MRP2第10外显子突变检出率分别为22.67%(17/75)和18.64%(22/118),第31外显子突变检出率分别为5.33%(4/75)和2.54%(3/118),两组基因突变率比较,差异均无统计学意义(x2值分别为0.312、1.165、0.460、2.794,P＞0.05).调整年龄、性别、吸烟、饮酒、果蔬摄入、肉蛋奶摄入和农药接触史后,以上基因突变率在两组间比较,差异仍无统计学意义(OR值分别为0.803、1.892、2.388、1.098,P＞0.05).结论 未发现MRP1基因第2、17、23外显子和MRP2基冈第10、18、31外显子突变对地方性砷中毒表型有影响.

abstractsObjective To explore the effect of gene mutations of arsenic transport proteins-muhidrug resistance-associated proteins(MRP1 and MRP2)on phenotype of endemic arsenic poisoning.Methods Two hundreds and thirty-nine rural residents in 3 villages of Shuocheng Region,Shanxi Province were interviewed and examined by simple random sampling who had been lived there for 20 yearn at least.All the objects were divided into two groups on the basis of clinical examination with"The Standard Diagnosis of Endemic Arsenic Poisoning" (WT/S 211-2001):subjectives with skin lesion as a arsenic poisoning group and without skin lesion as a control group. One hundred and ninety-three blood samples were collected from each participanL Seventy-five arsenic poisoning cases and 118 controls were detected the gene mutations in the 2,17,23 exons of M RPI and the 10,18,31 exons of MRP2 by PCR-single strand conformation polymorphism (PCR-SSCP) and compared by multivariate Logistic regression model. Results Seventy-five cases and 164 controls underwent questionnaires. Age[ (58.85±11.26) vs (45.73±11.92),OR = 3.378,P ＜ 0.05],gender[male,57.3%(43/75)vs 27.4%(45/164),OR = 3.553,P＜ 0.01 ],smoking[46.7%(35/75) vs 21.3%(35/164),OR = 3.225,P ＜ 0.01 ],drinking[ 17.3%(13/75) vs 8.5% (14/164),OR = 1.836,P ＞ 0.05],vegetable and fruit intake[5.3%(4/75) vs 9.1%(15/164),OR = 0.560,P ＞ 0.05],egg and meat intake[34.7%(26/75) vs 30.5%(50/164),OR = 1.210,P ＞ 0.05],exposure of pesticide [41.3%(31/75) vs 29.3%(48/164),OR = 1.864,P ＜ 0.05] were tested by Logistic regression model. There was no gene mutation detected in the 23 exon of MRP1 and the 18 exon of MRP2. The gene mutations frequencies of the 2 exons of MRP1 in arsenic poisoning and control groups were 8.00% (6/75) and 5.93% (7/118),respectively;they were 13.33%(10/75) and 8.47%(10/118) of the 17 exons of MRP1,respectively;they were 22.67%(17/75) and 18.64%(22/118) of the 10 exons of MRP2,respectively;they were 5.33%(4/75) and 2.54%(3/118) of the 31 exons of MRP2,respectively. There was no significant difference between two groups(x2 = 0.312,1.165,0.460, 2.794,respectively,all P ＞ 0.05). After age,gender,smoking,drinking,nutritional level and exposure of pesticide being adjusted by multivariate Logistic regression model,there was no significant difference between two groups (OR = 0.803,1.892,2.388,1.098,respectively,all P ＞ 0.05). Conclusions The gene mutations of 2,17,23 exons of MRPI and the 10,18,31 exons of MRP2 may have no effect on the phenotype of endemic arsenic poisoning.