300Association between rs2231142 of ABCG2 and gout, hyperuricemia and uric acid: Systematic review and meta-analysis

Abstract

Abstract Background Genome-wide association studies showed that rs2231142 (C421A) of ABCG2 gene has strong effects on gout and uric acid (UA). However, replication studies showed conflicting results. We aimed to pool effects of rs2231142 on gout, hyperuricemia, and UA across studies. Methods Studies were located from MEDLINE and Scopus until 17th June 2018. Data extractions were performed by two independent reviewers. Hardy-Weinberg equilibrium was checked. Genotype effects were pooled by ethnicity using mixed-effect logistic model for gout and hyperuricemia and multivariate meta-analysis for UA. Publication bias was assessed using funnel plots and Egger’s tests. Results Thirty studies were eligible; 21, 5, and 8 studies assessed association between rs2231142 and gout, hyperuricemia, and UA, respectively. Carrying AA and CA genotypes were 3.2 (2.4, 4.4) and 1.6 (1.5, 1.8) higher odds to develop gout in Caucasians. Likewise, in Asians, the ORs for corresponding genotypes were 4.5 (4.1, 5.0) and 2.1 (2.0, 2.3) for gout; 2.3 (1.8, 2.8) and 1.6 (1.4, 1.8) for hyperuricemia. Mean differences of UA in Caucasians carrying AA and CA were 50.4 (32.7, 68.2) and 19.5 (14.2, 24.7) µmol/l compared with those carrying CC genotype while in Asians, they were 18.4 (8.7, 28.1) and 11.5 (4.1, 18.9) µmol/l, respectively. Additive gene effects were suggested. Conclusions Significant effects of rs2231142 on gout, hyperuricemia, and elevated UA were confirmed. Our findings should be useful in personalized risk scores for prediction of gout and diseases related to high UA. Key messages rs2231142 increased the risk of gout and UA in Asians and Caucasians