Rasheed Humaira, Phipps-Green Amanda J, Topless Ruth, Smith Malcolm D, Hill Catherine, Lester Susan, Rischmueller Maureen, Janssen Matthijs, Jansen Timothy L, Joosten Leo A, Radstake Timothy R, Riches Philip L, Tausche Anne-Kathrin, Lioté Frederic, So Alexander, van Rij Andre, Jones Gregory T, McCormick Sally P, Harrison Andrew A, Stamp Lisa K, Dalbeth Nicola, Merriman Tony R
Department of Biochemistry, University of Otago, Dunedin, New Zealand Department of Chemistry, University of Engineering and Technology, Lahore, Pakistan.
Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Rheumatology (Oxford). 2016 Aug;55(8):1421-30. doi: 10.1093/rheumatology/kew057. Epub 2016 Apr 18.
Gout is associated with dyslipidaemia. Association of the apolipoprotein A1-C3-A4 gene cluster with gout has previously been reported in a small study. To investigate a possible causal role for this locus in gout, we tested the association of genetic variants from APOA1 (rs670) and APOC3 (rs5128) with gout.
We studied data for 2452 controls and 2690 clinically ascertained gout cases of European and New Zealand Polynesian (Māori and Pacific) ancestry. Data were also used from the publicly available Atherosclerosis Risk in Communities study (n = 5367) and the Framingham Heart Study (n = 2984). Multivariate adjusted logistic and linear regression was used to test the association of single-nucleotide polymorphisms with gout risk, serum urate, triglyceride and high-density lipoprotein cholesterol (HDL-C).
In Polynesians, the T-allele of rs670 (APOA1) increased (odds ratio, OR = 1.53, P = 4.9 × 10(-6)) and the G-allele of rs5128 (APOC3) decreased the risk of gout (OR = 0.86, P = 0.026). In Europeans, there was a strong trend to a risk effect of the T-allele for rs670 (OR = 1.11, P = 0.055), with a significant protective effect of the G-allele for rs5128 being observed after adjustment for triglycerides and HDL-C (OR = 0.81, P = 0.039). The effect at rs5128 was specific to males in both Europeans and Polynesians. Association in Polynesians was independent of any effect of rs670 and rs5128 on triglyceride and HDL-C levels. There was no evidence for association of either single-nucleotide polymorphism with serum urate levels (P ⩾ 0.10).
Our data, replicating a previous study, supports the hypothesis that the apolipoprotein A1-C3-A4 gene cluster plays a causal role in gout.
痛风与血脂异常相关。此前一项小型研究报道了载脂蛋白A1-C3-A4基因簇与痛风的关联。为了研究该基因座在痛风中可能的因果作用，我们检测了载脂蛋白A1（APOA1，rs670）和载脂蛋白C3（APOC3，rs5128）的基因变异与痛风的关联。
我们研究了2452名对照者以及2690例经临床确诊的痛风患者的数据，这些患者来自欧洲以及新西兰的波利尼西亚人（毛利人和太平洋岛民）。数据还来自公开可用的社区动脉粥样硬化风险研究（n = 5367）和弗雷明汉心脏研究（n = 2984）。采用多变量调整的逻辑回归和线性回归来检测单核苷酸多态性与痛风风险、血清尿酸、甘油三酯和高密度脂蛋白胆固醇（HDL-C）的关联。
在波利尼西亚人中，rs670（APOA1）的T等位基因增加了痛风风险（优势比，OR = 1.53，P = 4.9×10⁻⁶），而rs5128（APOC3）的G等位基因降低了痛风风险（OR = 0.86，P = 0.026）。在欧洲人中，rs670的T等位基因有增加风险的强烈趋势（OR = 1.11，P = 0.055），在调整甘油三酯和HDL-C后，观察到rs5128的G等位基因有显著的保护作用（OR = 0.81，P = 0.039）。rs5128的作用在欧洲人和波利尼西亚人中均对男性具有特异性。波利尼西亚人中的关联独立于rs670和rs5128对甘油三酯和HDL-C水平的任何影响。没有证据表明这两种单核苷酸多态性与血清尿酸水平有关联（P⩾0.10）。
我们的数据重复了之前的一项研究，支持载脂蛋白A1-C3-A4基因簇在痛风中起因果作用的假说。
