Abstract：
BACKGROUND: Childhood exposure to polycyclic aromatic hydrocarbons (PAHs) or lead (Pb) is associated with epigenetic modifications. However, the effects of their co-exposures on IGF1 (Insulin-like growth factor 1) methylation and the potential role in child physical growth are unclear.
METHODS: From our previous children study (N = 238, ages of 3-6), 75 children with higher total concentrations of urinary ten hydroxyl PAH metabolites (∑10OH-PAHs) from an e-waste recycling area, Guiyu, and 75 with lower ∑10OH-PAHs from Haojiang (reference area) were included. Pb and IGF1 P2 promoter methylation in peripheral blood were also measured. Multivariable linear regression analyses were performed to estimate individual associations, overall effects and interactions of co-exposure to OH-PAHs and Pb on IGF1 methylation were further explored using Bayesian kernel machine regression.
RESULTS: Methylation of IGF1 (CG-232) was lower (38.00 vs. 39.74 %, P < 0.001), but of CG-207 and CG-137 were higher (59.94 vs. 58.41 %; 57.60 vs. 56.28 %, both P < 0.05) in exposed children than the reference. The elevated urinary 2-OHPhe was associated with reduced methylation of CG-232 (B = -0.051, 95 % CI: -0.096, -0.005, P < 0.05), whereas blood Pb was positively associated with methylation of CG-108 (B = 0.106, 95 %CI: 0.013, 0.199, P < 0.05), even after full adjustment. Methylations of CG-224 and 218 significantly decreased when all OH-PAHs and Pb mixtures were set at 35th - 40th and 45th - 55th percentile compared to when all fixed at 50th percentile. There were bivariate interactions of co-exposure to the mixtures on methylations of CG-232, 224, 218, and 108. Methylations correlated with height, weight, were observed in the exposed children.
CONCLUSIONS: Childhood co-exposure to high PAHs and Pb from the e-waste may be associated with IGF1 promoter methylation alterations in peripheral blood. This, in turn, may interrupt the physical growth of preschool children.
METHODS: From our previous children study (N = 238, ages of 3-6), 75 children with higher total concentrations of urinary ten hydroxyl PAH metabolites (∑10OH-PAHs) from an e-waste recycling area, Guiyu, and 75 with lower ∑10OH-PAHs from Haojiang (reference area) were included. Pb and IGF1 P2 promoter methylation in peripheral blood were also measured. Multivariable linear regression analyses were performed to estimate individual associations, overall effects and interactions of co-exposure to OH-PAHs and Pb on IGF1 methylation were further explored using Bayesian kernel machine regression.
RESULTS: Methylation of IGF1 (CG-232) was lower (38.00 vs. 39.74 %, P < 0.001), but of CG-207 and CG-137 were higher (59.94 vs. 58.41 %; 57.60 vs. 56.28 %, both P < 0.05) in exposed children than the reference. The elevated urinary 2-OHPhe was associated with reduced methylation of CG-232 (B = -0.051, 95 % CI: -0.096, -0.005, P < 0.05), whereas blood Pb was positively associated with methylation of CG-108 (B = 0.106, 95 %CI: 0.013, 0.199, P < 0.05), even after full adjustment. Methylations of CG-224 and 218 significantly decreased when all OH-PAHs and Pb mixtures were set at 35th - 40th and 45th - 55th percentile compared to when all fixed at 50th percentile. There were bivariate interactions of co-exposure to the mixtures on methylations of CG-232, 224, 218, and 108. Methylations correlated with height, weight, were observed in the exposed children.
CONCLUSIONS: Childhood co-exposure to high PAHs and Pb from the e-waste may be associated with IGF1 promoter methylation alterations in peripheral blood. This, in turn, may interrupt the physical growth of preschool children.
摘要：
背景：儿童接触多环芳烃（PAHs）或铅（Pb）与表观遗传修饰有关。然而,他们共同暴露对IGF1(胰岛素样生长因子1)甲基化的影响以及在儿童体格发育中的潜在作用尚不清楚.
方法：根据我们之前的儿童研究（N=238，3-6岁），75名来自电子废物回收区的尿中10种羟基PAH代谢物（∑10OH-PAHs）总浓度较高的儿童，贵玉,包括75个来自豪江（参考区）的∑10OH-PAHs较低的PAHs。还测量了外周血中Pb和IGF1P2启动子甲基化。进行多变量线性回归分析以估计个体关联，使用贝叶斯核机回归进一步探讨了OH-PAHs和Pb共暴露对IGF1甲基化的总体影响和相互作用。
结果：IGF1（CG-232）的甲基化较低（38.00vs.39.74%,P<0.001)，但CG-207和CG-137的比例更高(59.94vs.58.41%；57.60vs.56.28%，两者P<0.05)在暴露儿童中都比参考儿童高。尿2-OHP升高与CG-232甲基化降低相关(B=-0.051,95%CI:-0.096,-0.005,P<0.05),而血铅与CG-108甲基化呈正相关(B=0.106,95CI:0.013,0.199,P<0.05),即使经过全面调整。当所有OH-PAHs和Pb混合物均设定在第35-40和第45-55百分位时，与全部固定在第50百分位时相比，CG-224和218的甲基化显着降低。在CG-232、224、218和108的甲基化上，共暴露于混合物存在双变量相互作用。甲基化与身高相关，体重,在暴露的儿童中观察到。
结论：儿童共同暴露于来自电子废物的高PAHs和Pb可能与外周血IGF1启动子甲基化改变有关。这个,反过来,可能会中断学龄前儿童的身体发育。
方法：根据我们之前的儿童研究（N=238，3-6岁），75名来自电子废物回收区的尿中10种羟基PAH代谢物（∑10OH-PAHs）总浓度较高的儿童，贵玉,包括75个来自豪江（参考区）的∑10OH-PAHs较低的PAHs。还测量了外周血中Pb和IGF1P2启动子甲基化。进行多变量线性回归分析以估计个体关联，使用贝叶斯核机回归进一步探讨了OH-PAHs和Pb共暴露对IGF1甲基化的总体影响和相互作用。
结果：IGF1（CG-232）的甲基化较低（38.00vs.39.74%,P<0.001)，但CG-207和CG-137的比例更高(59.94vs.58.41%；57.60vs.56.28%，两者P<0.05)在暴露儿童中都比参考儿童高。尿2-OHP升高与CG-232甲基化降低相关(B=-0.051,95%CI:-0.096,-0.005,P<0.05),而血铅与CG-108甲基化呈正相关(B=0.106,95CI:0.013,0.199,P<0.05),即使经过全面调整。当所有OH-PAHs和Pb混合物均设定在第35-40和第45-55百分位时，与全部固定在第50百分位时相比，CG-224和218的甲基化显着降低。在CG-232、224、218和108的甲基化上，共暴露于混合物存在双变量相互作用。甲基化与身高相关，体重,在暴露的儿童中观察到。
结论：儿童共同暴露于来自电子废物的高PAHs和Pb可能与外周血IGF1启动子甲基化改变有关。这个,反过来,可能会中断学龄前儿童的身体发育。
