铝电解工人血铝水平与APP基因甲基化的关系

Association between serum aluminium level and methylation of amyloid precursor protein gene in workers engaged in aluminium electrolysis

目的 探讨铝电解工人血铝浓度与淀粉样前体蛋白（APP）基因启动子区甲基化之间的关系.方法 于2012年选择某铝厂电解工366名为暴露组（工龄＞10年,年龄＞40岁）,以血铝浓度中位数为界将铝电解工人分为低暴露组和高暴露组;同时选择未接触铝的水泥厂工人102名为对照组.采用石墨炉原子吸收分光光度法测定血铝水平,采用甲基化特异性聚合酶链式反应检测APP基因启动子区的甲基化率,采用酶联免疫吸附测定（ELISA）法测定外周血中淋巴细胞APP蛋白的表达水平.结果 暴露组工人血铝水平（45.07 μg/L）明显高于对照组（30.51 μg/L）,差异有统计学意义（P＜0.01）.暴露组的APP基因启动子区甲基化率（18.85％）较对照组（25.49％）明显降低,差异有统计学意义（P＜0.05）;高暴露组APP基因启动子区甲基化率（15.84％）明显低于低暴露组（21.85％）,差异有统计学意义（P＜0.05）.暴露组工人外周血中淋巴细胞APP蛋白表达量（66.73 ng/ml）明显高于对照组（54.17 ng/ml）,差异有统计学意义（P＜0.05）;与低暴露组（65.39 ng/ml）比较,高暴露组工人外周血中淋巴细胞APP蛋白表达量（67.22 ng/ml）增高,但差异无统计学意义（P＞0.05）.多元logistic回归分析显示,以对照组为参照,低铝暴露是发生APP基因启动子区甲基化率降低的危险因素（OR=1.86,95％CI：1.67～3.52）,高铝暴露也是发生APP基因启动子区甲基化率降低的危险因素（OR =2.98,95％CI：1.97～4.15）.结论APP基因启动子区甲基化水平降低可能与血铝浓度增高有关,而APP基因启动子区甲基化水平下调,可能加速APP基因的转录.

Objective To investigate the association between serum aluminium level and methylation of the promoter region of amyloid precursor protein （APP） gene in workers engaged in aluminium electrolysis.Methods In 2012,366 electrolysis workers in an aluminium factory were enrolled as exposure group （working years 〉10 and age 〉40 years） and divided into low-exposure group and high-exposure group based on the median serum aluminium level.Meanwhile,102 workers in a cement plant not exposed to aluminium were enrolled as control group.Graphite furnace atomic absorption spectrometry was used to measure serum aluminium level,methylation specific PCR was used to measure the methylation rate of the promoter region of APP gene,and ELISA was used to measure the protein expression of APP in lymphocytes in peripheral blood.Results The exposure group had a significantly higher serum aluminium level than the control group（45.07 μg/L vs 30.51 μg/L,P〈0.01）.The exposure group had a significantly lower methylation rate of the promoter region of APP gene than the control group （18.85% vs 25.49%,P=0.025）,and the high-exposure group had a significantly lower methylation rate of the promoter region of APP gene than the low-exposure group （15.84% vs 21.85%,P〈0.05）.The exposure group had a significantly higher protein expression of APP in lymphocytes in peripheral blood than the control group （66.73 ng/ml vs 54.17 ng/ml,P〈0.05）;compared with the low-exposure group （65.39 ng/ml）,the high-exposure group showed an increase in the protein expression of APP in lymphocytes in peripheral blood （67.22 ng/ml）,but there was no significant difference between these two groups （P〉0.05）.The multivariate logistic regression analysis showed that with reference to the control group,low aluminium exposure （OR=1.86,95%CI 1.67～3.52） and high aluminium exposure （OR=2.98,95%CI 1.97～4.15） were risk factors for a reduced methylation rate of the promoter region of APP gene.Conclusion Reduced methylation of the promoter region of APP gene may be associated with increased serum aluminium level,and downregulated methylation of the promoter region of APP gene may accelerate APP gene transcription.