燃煤型砷中毒患者砷甲基化代谢与皮肤、肝脏损害相关性

Correlation between arsenic methylation metabolism and skin and liver damage in patients with coal-burning arsenism

目的分析燃煤型砷中毒人群尿砷甲基化代谢水平,探讨其与砷中毒皮肤和肝脏损害的关系。方法以贵州省黔西南州雨樟燃煤污染型砷中毒病区为调查点,筛选符合《地方性砷中毒诊断》(WS/T 211—2015)标准的202例燃煤型砷中毒患者,根据皮肤损伤诊断标准分为皮肤损害轻度组(48例)、中度组(70例)和重度组(84例);选择距该病区12 km外无燃用高砷煤史、且生活习惯相近的56名健康居民作为对照组。以肝功能指标白蛋白(ALB)、白蛋白与球蛋白比值(A/G)反映砷中毒人群肝损害情况。采用高效液相色谱–电感耦合等离子体质谱(HPLC-ICP-MS)检测调查对象尿中三价砷(As^(3+))、五价砷(As^(5+))、一甲基砷(MMA)和二甲基砷(DMA)水平,以As^(3+)、As^(5+)、MMA和DMA含量加和算作总砷(tAs),并计算其百分占比(As^(3+)%、As^(5+)%、MMA%、DMA%)、一甲基化率(PMI)和二甲基化率(SMI)。结果与对照组比较,砷中毒人群尿As^(3+)、MMA含量和As^(3+)%、MMA%显著升高(P<0.05),DMA%、PMI、SMI显著降低(P<0.05);砷中毒皮肤损害轻、中、重度组人群尿中As^(3+)%明显升高(P<0.05),DMA%、PMI、SMI明显降低(P<0.05);砷中毒人群随皮肤损害程度加重,尿中As^(3+)%、MMA%逐渐升高,SMI逐渐下降(P<0.05)。与对照组比较,砷中毒人群血清ALB和A/G明显降低(P<0.05);随尿中As^(3+)%、MMA%升高和DMA%、PMI、SMI降低,ALB水平明显下降(P<0.05);A/G随尿中As^(3+)%升高呈下降趋势(P<0.05)。As^(3+)%、MMA%的曲线下面积(AUC)分别为0.84、0.63,两指标联合应用的AUC为0.82;As^(3+)%、MMA%最佳界值分别为14.37%(特异度83.93%,灵敏度73.27%)、12.10%(特异度73.21%,灵敏度50.99%),两指标联合应用的特异度为89.29%,灵敏度为66.83%。结论燃煤型砷中毒人群甲基化代谢能力减弱是砷致皮肤和肝脏损害的危险因素;As^(3+)%、MMA%可作为评估燃煤型砷中毒的潜在指标,两者联合应用可提高特异性。

Objective To analyze the level of urinary arsenic methylation metabolism and its correlation with skin and liver damage among coal-burning arsenism patients.Methods Based on the“Diagnostic Criteria of Endemic Arsenism”(WS/T 211—2015)issued by Health and Family Planning Commission of the People′s Republic of China,we recruited 202 arsenism patients in an endemic area with arsenic pollution caused by coal-burning in southwestern region of Guizhou province and subdivided the patients into a mild(n=48),moderate(n=70)and severe group(n=84)according to the severity of skin damage of the patients.The controls of the study were 56 healthy residents recruited in a region 12 kilometers away from the endemic arsenism area and the controls had everyday life similar to that of patients and no history of exposure to burning high arsenic coal.Serum albumin(ALB)and albumin/globulin(A/G)ratio were used to assess liver damage of the participants.High performance liquid chromatography-inductively coupled plasma mass spectrometry(HPLC-ICPMS)was adopted to detect trivalent arsenic(As^(3+)),pentavalent arsenic(As^(5+)),monomethyl arsenic(MMA)and dimethyl arsenic(DMA)in the urine samples of the participants and the detection results were used to calculate total arsenic(tAS),proportions of As^(3+),As^(5+),MMA and DMA(As^(3+)%,As^(5+)%,MMA%and DMA%),primary methylation index(PMI),and the secondary methylation index(SMI).Results Compared to the controls,the arsenism patients had significantly increased urinary As^(3+),MMA,As^(3+)%and MMA%(P<0.05 for all)but decreased DMA%,PMI and SMI(all P<0.05).The patients′urinary As^(3+)%and MMA%increased and SMI decreased significantly with the severity of skin damage(P<0.05 for all).In the arsenism patients,the serum ALB and A/G decreased significantly in comparison with those in the controls(both P<0.05);the serum ALB declined with the increase of urinary As^(3+)%and MMA%and the decrease of urinary DMA%,PMI and SMI(all P<0.05),while with the increase of urinary As^(3+)%the serum A/G declined significantly(P<0.05).When used as two indicators for the assessment of arsenism,the urinary As^(3+)%and MMA%presented the area under the receiver operating characteristic curve(AUC)of 0.84 and 0.63 and the optimal cutoff point of 14.37%and 12.10%;the specificity of the two cutoff points were 83.93%and 73.21%and the sensitivity of the two cutoff points were 73.27%and 50.99%.When combining As^(3+)%and MMA%as an integrated indicator,the indicator′s AUC was 0.82,with a specificity of 89.29%and a sensitivity of 66.83%,respectively.Conclusion Attenuated arsenic methylation metabolism is a risk factor for skin and liver damage among coal-burning arsenism patients.Urinary As^(3+)%and MMA%could be used as potential indicators for the assessment of coal-burning arsenism and the assessment specificity increases when the two indicators being combined.