Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Programs in Metabolism and Medical & Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Arthritis Res Ther. 2021 Mar 4;23(1):75. doi: 10.1186/s13075-021-02444-8.
Prevention of hyperuricaemia (HU) is critical to the prevention of gout. Understanding causal relationships and relative contributions of various risk factors to hyperuricemia is therefore important in the prevention of gout. Here, we use attributable fraction to compare the relative contribution of genetic, dietary, urate-lowering therapy (ULT) and other exposures to HU. We use Mendelian randomisation to test for the causality of diet in urate levels.
Four European-ancestry sample sets, three from the general population (n = 419,060) and one of people with gout (n = 6781) were derived from the Database of Genotypes and Phenotypes (ARIC, FHS, CARDIA, CHS) and UK Biobank. Dichotomised exposures to diet, genetic risk variants, BMI, alcohol, diuretic treatment, sex and age were used to calculate adjusted population and average attributable fractions (PAF/AAF) for HU (≥0.42 mmol/L [≥7 mg/dL]). Exposure to ULT was also assessed in the gout cohort. Two sample Mendelian randomisation was done in the UK Biobank using dietary pattern-associated genetic variants as exposure and serum urate levels as outcome.
Adherence to dietary recommendations, BMI (< 25 kg/m), and absence of the SLC2A9 rs12498742 urate-raising allele produced PAFs for HU of 20 to 24%, 59 to 69%, and 57 to 64%, respectively, in the three non-gout cohorts. In the gout cohort, diet, BMI, SLC2A9 rs12498742 and ULT PAFs for HU were 12%, 49%, 48%, and 63%, respectively. Mendelian randomisation demonstrated weak causal effects of four dietary habits on serum urate levels (e.g. preferentially drinking skim milk increased urate, β = 0.047 mmol/L, P = 3.78 × 10). These effects were mediated by BMI, and they were not significant (P ≥ 0.06) in multivariable models assessing the BMI-independent effect of diet on urate.
Diet has a relatively minor role in determining serum urate levels and HU. In gout, the use of ULT was the largest attributable fraction tested for HU.
预防高尿酸血症（HU）对于预防痛风至关重要。因此，了解各种风险因素对高尿酸血症的因果关系和相对贡献对于预防痛风非常重要。在这里，我们使用归因分数来比较遗传、饮食、尿酸降低治疗（ULT）和其他暴露因素对 HU 的相对贡献。我们使用孟德尔随机化来检验饮食对尿酸水平的因果关系。
从基因型和表型数据库（ARIC、FHS、CARDIA、CHS）和英国生物库中提取了四个欧洲血统样本集，其中三个来自普通人群（n=419060），一个来自痛风患者（n=6781）。将饮食、遗传风险变异、BMI、酒精、利尿剂治疗、性别和年龄的二分暴露用于计算 HU（≥0.42mmol/L [≥7mg/dL]）的调整人群和平均归因分数（PAF/AAF）。在痛风队列中还评估了 ULT 的暴露情况。在英国生物库中使用饮食模式相关的遗传变异作为暴露，血清尿酸水平作为结局，进行了两样本孟德尔随机化。
在三个非痛风队列中，遵循饮食建议、BMI（<25kg/m）和不存在 SLC2A9 rs12498742 尿酸升高等位基因分别产生 HU 的 PAF 为 20%至 24%、59%至 69%和 57%至 64%。在痛风队列中，饮食、BMI、SLC2A9 rs12498742 和 ULT 对 HU 的 PAF 分别为 12%、49%、48%和 63%。孟德尔随机化显示，四种饮食习惯对血清尿酸水平有微弱的因果影响（例如，优先饮用脱脂牛奶会增加尿酸，β=0.047mmol/L，P=3.78×10）。这些影响通过 BMI 介导，并且在多变量模型中评估饮食对尿酸的 BMI 独立影响时不显著（P≥0.06）。
饮食在决定血清尿酸水平和 HU 方面的作用相对较小。在痛风中，ULT 的使用是针对 HU 测试的最大归因分数。
