Department of Epidemiology and Statistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China.
State Key Laboratory of Common Mechanism Research for Major Diseases, Beijing, China.
Ann Med. 2024 Dec;56(1):2434186. doi: 10.1080/07853890.2024.2434186. Epub 2024 Nov 28.
We aim to investigate the joint effect of triglyceride-glucose (TyG) index and polygenic risk scores (PRS) of urate transporter genes and on hyperuricemia.
Baseline data from two prospective population-based cohort studies, including 30,453 individuals aged 50 years or older, were used to analyze the association between TyG index and hyperuricemia. A case-control study was then designed from the cohorts to investigate the interaction between genetic predisposition and TyG index on hyperuricemia among 595 matched pairs. PRS was constructed using 14 single nucleotide polymorphisms located in the and genes.
In both sexes, higher TyG index levels were correlated with elevated serum urate (SUA) levels ( values in both sexes < 0.001). In men, per unit increase of TyG was associated with a 1.44-fold (95% confidence interval [CI]: 1.35-1.55) higher risk of hyperuricemia after adjusted for covariates. In women, this estimate was 1.69 (1.51-1.89). Demonstrated by the restrict cubic spline model, TyG index was both linearly and non-linearly associated with elevated SUA (both values < 0.001). Association between TyG index and hyperuricemia was stronger among people with higher genetic risk, and vice versa. Compared to people with TyG < 9 and PRS < 2, the odds ratios (ORs) (95% CIs) for hyperuricemia in the TyG <9 but PRS ≥2, TyG ≥9 but PRS < 2, TyG ≥9 and PRS ≥2 groups were 3.30 (1.53-7.14), 3.16 (1.23-8.11) and 7.55 (2.76-20.65), respectively. Additive interaction was also significant, with 57.5% (30.5%-84.4%) of the excess risk attributable to the additive gene-TyG index interaction.
The impact of genetic predisposition on hyperuricemia was significantly greater among individuals with a higher TyG index. Over 50% of the increased risk can be attributed to the interaction, indicating a crucial synergy between genetic factors and TyG index when estimating hyperuricemia risk.
本研究旨在探讨甘油三酯-葡萄糖（TyG）指数与尿酸转运体基因多基因风险评分（PRS）对高尿酸血症的联合影响。
本研究使用来自两项前瞻性基于人群的队列研究的基线数据，共纳入 30453 名年龄在 50 岁及以上的个体，分析 TyG 指数与高尿酸血症之间的关联。然后，从这些队列中设计了一项病例对照研究，以调查遗传易感性与 TyG 指数对 595 对匹配个体高尿酸血症的交互作用。PRS 是使用位于 和 基因中的 14 个单核苷酸多态性构建的。
在男性和女性中，更高的 TyG 指数水平与血清尿酸（SUA）水平升高相关（两性中 值均<0.001）。在男性中，TyG 每增加一个单位，高尿酸血症的风险增加 1.44 倍（95%置信区间[CI]：1.35-1.55），校正协变量后。在女性中，这一估计值为 1.69（1.51-1.89）。限制立方样条模型表明，TyG 指数与升高的 SUA 呈线性和非线性相关（均 值<0.001）。在遗传风险较高的人群中，TyG 指数与高尿酸血症之间的关联更强，反之亦然。与 TyG<9 和 PRS<2 的人群相比，TyG<9 但 PRS≥2、TyG≥9 但 PRS<2、TyG≥9 且 PRS≥2 组高尿酸血症的比值比（ORs）（95%CI）分别为 3.30（1.53-7.14）、3.16（1.23-8.11）和 7.55（2.76-20.65）。加性交互作用也具有统计学意义，遗传因素与 TyG 指数相互作用导致的超额风险有 57.5%（30.5%-84.4%）归因于此。
遗传易感性对高尿酸血症的影响在 TyG 指数较高的个体中更为显著。超过 50%的风险增加归因于交互作用，表明在估计高尿酸血症风险时，遗传因素和 TyG 指数之间存在重要的协同作用。
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