Department of Occupational and Environmental Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Department of Occupational and Environmental Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Int J Hyg Environ Health. 2024 Apr;257:114342. doi: 10.1016/j.ijheh.2024.114342. Epub 2024 Feb 23.
Growing evidences supported that arsenic exposure contributes to non-alcoholic fatty liver disease (NAFLD) risk, but findings were still inconsistent. Additionally, once absorbed, arsenic is methylated into monomethyl and dimethyl arsenicals. However, no studies investigated the association of arsenic metabolism with NAFLD. Our objectives were to evaluate the associations of arsenic exposure and arsenic metabolism with NAFLD prevalence. We conducted a case-control study with 1790 participants derived from Dongfeng-Tongji cohort and measured arsenic species (arsenite, arsenate, monomethylarsonate [MMA], dimethylarsinate [DMA], and arsenobetaine) in urine. Arsenic exposure (∑As) was defined as the sum of inorganic arsenic (iAs), MMA, and DMA. Arsenic metabolism was evaluated as the proportions of inorganic-related species (iAs%, MMA%, and DMA%) and methylation efficiency ratios (primary methylation index [PMI], secondary methylation index [SMI]). NAFLD was diagnosed by liver ultrasound. Logistic regression was used to evaluate the associations. The median of ∑As was 13.24 μg/g creatinine. The ∑As showed positive and nonlinear association with moderate/severe NAFLD (OR: per log-SD = 1.33, 95% CI: [1.03,1.71]; P = 0.021). The iAs% (OR: per SD = 1.16, 95% CI: [1.03,1.30]) and SMI (OR: per log-SD = 1.16, 95% CI: [1.03,1.31]) showed positive while MMA% (OR: per SD = 0.80, 95% CI: [0.70,0.91]) and PMI (OR: per log-SD = 0.86, 95% CI: [0.77,0.96]) showed inverse associations with NAFLD. Moreover, the ORs (95% CI) of NAFLD for each 5% increase in iAs% was 1.36 (1.17,1.58) when MMA% decreased and 1.07 (1.01,1.13) when DMA% decreased; and for each 5% increase in MMA%, it was 0.74 (0.63,0.86) and 0.79 (0.69,0.91) when iAs% and DMA% decreased, respectively. The results suggest that inorganic arsenic exposure is positively associated with NAFLD risk and arsenic methylation efficiency plays a role in the NAFLD. The findings provide clues to explore potential interventions for the prevention of NAFLD. Prospective studies are needed to validate our findings.
越来越多的证据表明，砷暴露会导致非酒精性脂肪性肝病（NAFLD）的风险，但研究结果仍不一致。此外，一旦被吸收，砷就会被甲基化为一甲基和二甲基砷酸盐。然而，目前尚无研究探讨砷代谢与 NAFLD 之间的关联。我们的目的是评估砷暴露和砷代谢与 NAFLD 患病率之间的关联。我们对东风-同济队列中的 1790 名参与者进行了病例对照研究，并测量了尿液中的砷形态（砷酸盐、亚砷酸盐、一甲基砷酸盐[MMA]、二甲基砷酸盐[DMA]和砷甜菜碱）。砷暴露（∑As）定义为无机砷（iAs）、MMA 和 DMA 的总和。砷代谢评估为无机相关物种（iAs%、MMA%和 DMA%）和甲基化效率比（初级甲基化指数[PMI]、次级甲基化指数[SMI]）的比例。NAFLD 通过肝脏超声诊断。使用 logistic 回归评估关联。∑As 的中位数为 13.24μg/g 肌酐。∑As 与中重度/重度 NAFLD 呈正相关且呈非线性关系（OR：每 log-SD 为 1.33，95%CI：[1.03，1.71]；P=0.021）。iAs%（OR：每 SD 为 1.16，95%CI：[1.03，1.30]）和 SMI（OR：每 log-SD 为 1.16，95%CI：[1.03，1.31]）呈正相关，而 MMA%（OR：每 SD 为 0.80，95%CI：[0.70，0.91]）和 PMI（OR：每 log-SD 为 0.86，95%CI：[0.77，0.96]）呈负相关与 NAFLD。此外，当 MMA%降低时，iAs%每增加 5%，NAFLD 的 OR（95%CI）为 1.36（1.17，1.58），当 DMA%降低时，OR（95%CI）为 1.07（1.01，1.13）；当 MMA%增加 5%时，当 iAs%和 DMA%降低时，OR（95%CI）分别为 0.74（0.63，0.86）和 0.79（0.69，0.91）。结果表明，无机砷暴露与 NAFLD 风险呈正相关，砷甲基化效率在 NAFLD 中起作用。这些发现为探索预防 NAFLD 的潜在干预措施提供了线索。需要前瞻性研究来验证我们的发现。
