一些研究发现多环芳烃(PAHs)与血清尿酸(SUA)或高尿酸血症(HUA)有关。然而,纵向研究是空缺的,和潜在的机制仍然不清楚。我们旨在评估尿PAHs代谢物与SUA水平和HUA风险的横截面和纵向关联,探讨氧化应激与炎症的中介作用。在基线时对4047名中国城市居民和6年随访时的1496名个体进行了10种尿单羟基化PAHs代谢产物和SUA水平的测定。在基线时测定尿/血浆中氧化损伤和炎症的生物标志物。我们采用广义线性混合模型和逻辑回归来评估PAHs代谢物与SUA和HUA的关联。加权分位数和回归和自适应弹性网络回归来评估多种PAHs混合物的整体效应,和中介分析,以估计生物标志物的中介作用。在横断面研究中,2-OHNa的ln变换值每增加1个单位,2-OHFlu,4-OHPh,9-OHPh,3-OHPh,2-OHPh,ΣOHNa,ΣOHPh,ΣOHPAHs与4.10-相关,3.90-,6.42-,7.33-,4.85-,5.43-,4.47-,7.67-,SUA增加5.22-μmol/L,分别。同时,1-OHNa的ln变换值每增加1个单位,2-OHNa,4-OHPh,9-OHPh,3-OHPh,2-OHPh,ΣOHNa,ΣOHPh,ΣOHPAHs与HUA风险增加17、14、15、22、14、19、18、27和21%相关,分别。6年后,与9-OHPh持续高水平的个体相比,9-OHPh持续高水平的个体SUA增加12.5μmol/L。多种PAHs混合物对SUA和HUA的总体影响仍然是积极的。8-羟基脱氧鸟苷介导PAHs代谢产物与SUA和HUA的关联,介导比例从5.39%到15.34%不等。PAHs暴露与SUA水平升高和HUA风险增加有关,氧化性DNA损伤可能是潜在机制之一。
A few studies found polycyclic aromatic hydrocarbons (PAHs) were associated with serum uric acid (SUA) or hyperuricemia (HUA). However, the longitudinal study is vacant, and the underlying mechanisms remain unclear. We aimed to assess the cross-sectional and longitudinal associations of urinary PAHs metabolites with SUA levels and HUA risk, and explore the mediating effects of oxidative stress and inflammation. 10 urinary mono-hydroxylated PAHs metabolites and SUA levels were measured among 4047 Chinese urban residents at baseline and 1496 individuals at 6-year follow-up. Biomarkers of oxidative damage and inflammation in urine/plasma were determined at baseline. We adopted generalized linear mixed models and logistic regression to assess the associations of PAHs metabolites with SUA and HUA, weighted quantile sum regression and adaptive elastic net regression to evaluate the overall effects of multi-PAHs mixture, and mediation analysis to estimate the mediating roles of the biomarkers. In the cross-sectional study, each 1-unit increase in the ln-transformed values of 2-OHNa, 2-OHFlu, 4-OHPh, 9-OHPh, 3-OHPh, 2-OHPh, ΣOHNa, ΣOHPh, and ΣOHPAHs was associated with a 4.10-, 3.90-, 6.42-, 7.33-, 4.85-, 5.43-, 4.47-, 7.67-, and 5.22-μmol/L increase in SUA, respectively. Meanwhile, each 1-unit increase in the ln-transformed values of 1-OHNa, 2-OHNa, 4-OHPh, 9-OHPh, 3-OHPh, 2-OHPh, ΣOHNa, ΣOHPh, and ΣOHPAHs was associated with a 17, 14, 15, 22, 14, 19, 18, 27, and 21% increment in HUA risk, respectively. After 6 years, individuals with persistent high level of 9-OHPh had a 12.5 μmol/L increase in SUA compared with those with persistent low level. The overall effects of multi-PAHs mixture on SUA and HUA remain positive. 8-hydroxy-deoxyguanosine mediated the associations of PAHs metabolites with SUA and HUA, and the mediated proportion ranged from 5.39% to 15.34%. PAHs exposure was associated with the elevated SUA levels and increased HUA risk, and oxidative DNA damage may be one of the underlying mechanisms.