Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota.
J Clin Endocrinol Metab. 2018 Nov 1;103(11):4005-4013. doi: 10.1210/jc.2018-00472.
Previous epidemiological studies had inconsistent results regarding the relationship between blood lead level (BLL) and adiposity.
We aimed to investigate the associations of BLL with body mass index (BMI) particularly using Mendelian randomization analyses and examine the interaction between obesity-predisposing genes and BLL on the associations.
A total of 3922 participants were enrolled from 16 sites in East China in 2014 from the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (ChiCTR-ECS-14005052, www.chictr.org.cn). We calculated the weighted BMI genetic risk score (GRS) based on 29 variants that were identified and validated in East Asians. BLL was measured by atomic absorption spectrometry.
BMI was calculated, and BMI ≥25 kg/m2 was defined as overweight.
Multivariable logistic regression analysis demonstrated significant associations between BMI with each unit increase in lnBLL (β = 0.24; 95% CI, 0.08 to 0.40; P < 0.001) and each 1-point increase in BMI-GRS (β = 0.08; 95% CI, 0.05 to 0.11; P < 0.001). The causal regression coefficients of genetically determined BMI for lnBLL were -0.003 (95% CI, -0.075 to 0.070), which showed no significance. The GRS modified the association of BLL with BMI and overweight (BMI ≥25 kg/m2; P for interaction = 0.031 and 0.001, respectively). Each unit of lnBLL was associated with 63% higher odds of overweight (OR 1.63; 95% CI, 1.30 to 2.05) in the highest quartile of GRS, but no significant associations were found in the lower three quartiles.
The associations of BLL with BMI and overweight (BMI ≥25 kg/m2) were significantly modulated by BMI genetic susceptibility.
先前的流行病学研究对于血铅水平（BLL）与肥胖之间的关系结果并不一致。
我们旨在通过孟德尔随机化分析研究 BLL 与体重指数（BMI）的关联，并探讨肥胖易感基因与 BLL 之间的相互作用对这些关联的影响。
2014 年，我们从中国东部的 16 个地点共招募了 3922 名参与者，参加了中国东部代谢性疾病及危险因素调查（ChiCTR-ECS-14005052，www.chictr.org.cn）。我们根据在东亚人群中鉴定和验证的 29 个变异，计算了基于 29 个变异的 BMI 遗传风险评分（GRS）。采用原子吸收光谱法测量 BLL。
计算 BMI，并将 BMI≥25kg/m2 定义为超重。
多变量 logistic 回归分析显示，BMI 与 lnBLL 每增加一个单位（β=0.24；95%CI，0.08 至 0.40；P<0.001）和 BMI-GRS 每增加 1 分（β=0.08；95%CI，0.05 至 0.11；P<0.001）均呈显著正相关。遗传决定的 BMI 对 lnBLL 的因果回归系数为-0.003（95%CI，-0.075 至 0.070），无统计学意义。GRS 改变了 BLL 与 BMI 和超重（BMI≥25kg/m2）的关联（交互作用 P 值分别为 0.031 和 0.001）。在 GRS 最高四分位数中，lnBLL 每增加一个单位与超重的比值比（OR）为 1.63（95%CI，1.30 至 2.05），超重的几率增加 63%；而在较低的三分位数中，没有发现显著的关联。
BLL 与 BMI 和超重（BMI≥25kg/m2）的关联受 BMI 遗传易感性的显著调节。
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