Rasheed Humaira, Stamp Lisa K, Dalbeth Nicola, Merriman Tony R
Biochemistry Department, University of Otago, 710 Cumberland Street, Box 56, Dunedin, 9054, New Zealand.
University of Engineering and Technology, Lahore, Pakistan.
Arthritis Res Ther. 2017 Jul 5;19(1):161. doi: 10.1186/s13075-017-1369-y.
Some gout-associated loci interact with dietary exposures to influence outcome. The aim of this study was to systematically investigate interactions between alcohol exposure and urate-associated loci in gout.
A total of 2792 New Zealand European and Polynesian (Māori or Pacific) people with or without gout were genotyped for 29 urate-associated genetic variants and tested for a departure from multiplicative interaction with alcohol exposure in the risk of gout. Publicly available data from 6892 European subjects were used to test for a departure from multiplicative interaction between specific loci and alcohol exposure for the risk of hyperuricemia (HU). Multivariate adjusted logistic and linear regression was done, including an interaction term.
Interaction of any alcohol exposure with GCKR (rs780094) and A1CF (rs10821905) influenced the risk of gout in Europeans (interaction term 0.28, P = 1.5 × 10; interaction term 0.29, P = 1.4 × 10, respectively). At A1CF, alcohol exposure suppressed the gout risk conferred by the A-positive genotype. At GCKR, alcohol exposure eliminated the genetic effect on gout. In the Polynesian sample set, there was no experiment-wide evidence for interaction with alcohol in the risk of gout (all P > 8.6 × 10). However, at GCKR, there was nominal evidence for an interaction in a direction consistent the European observation (interaction term 0.62, P = 0.05). There was no evidence for an interaction of A1CF or GCKR with alcohol exposure in determining HU.
These data support the hypothesis that alcohol influences the risk of gout via glucose and apolipoprotein metabolism. In the absence of alcohol exposure, genetic variants in the GCKR and A1CF genes have a stronger role in gout.
一些与痛风相关的基因座与饮食暴露相互作用以影响结果。本研究的目的是系统地调查酒精暴露与痛风中尿酸相关基因座之间的相互作用。
对总共2792名有或无痛风的新西兰欧洲人和波利尼西亚人（毛利人或太平洋岛民）进行29种尿酸相关基因变异的基因分型，并测试痛风风险与酒精暴露的相乘相互作用是否存在偏差。利用来自6892名欧洲受试者的公开数据，测试特定基因座与酒精暴露之间在高尿酸血症（HU）风险方面的相乘相互作用是否存在偏差。进行多变量调整的逻辑回归和线性回归，包括一个相互作用项。
在欧洲人中，任何酒精暴露与GCKR（rs780094）和A1CF（rs10821905）的相互作用影响痛风风险（相互作用项分别为0.28，P = 1.5×10；相互作用项为0.29，P = 1.4×10）。在A1CF基因座，酒精暴露抑制了A阳性基因型赋予的痛风风险。在GCKR基因座，酒精暴露消除了对痛风的遗传影响。在波利尼西亚样本组中，没有全实验范围的证据表明痛风风险与酒精存在相互作用（所有P > 8.6×10）。然而，在GCKR基因座，有名义上的证据表明存在与欧洲观察结果一致方向的相互作用（相互作用项为0.62，P = 0.05）。在确定HU方面，没有证据表明A1CF或GCKR与酒精暴露存在相互作用。
这些数据支持酒精通过葡萄糖和载脂蛋白代谢影响痛风风险的假设。在无酒精暴露的情况下，GCKR和A1CF基因中的遗传变异在痛风中作用更强。
