Abstract
BackgroundReplication studies showed conflicting effects of ABCG2 and SLC2A9 polymorphisms on gout and serum urate. This meta-analysis therefore aimed to pool their effects across studies.MethodsStudies were located from MEDLINE and Scopus from inception to 17th June 2018. Observational studies in adults with any polymorphism in ABCG2 or SLC2A9, and outcome including gout, hyperuricemia, and serum urate were included for pooling. Data extractions were performed by two independent reviewers. Genotype effects were pooled stratified by ethnicity using a mixed-effect logistic model and a multivariate meta-analysis for dichotomous and continuous outcomes.ResultsFifty-two studies were included in the analysis. For ABCG2 polymorphisms, mainly studied in Asians, carrying 1–2 minor-allele-genotypes of rs2231142 and rs72552713 were respectively about 2.1–4.5 and 2.5–3.9 times higher odds of gout than non-minor-allele-genotypes. The two rs2231142-risk-genotypes also had higher serum urate about 11–18 μmol/l. Conversely, carrying 1–2 minor alleles of rs2231137 was about 36–57% significantly lower odds of gout. For SLC2A9 polymorphisms, mainly studied in Caucasians, carrying 1–2 minor alleles of rs1014290, rs6449213, rs6855911, and rs7442295 were about 25–43%, 31–62%, 33–64%, and 35–65% significantly lower odds of gout than non-minor-allele-genotypes. In addition, 1–2 minor-allele-genotypes of the latter three polymorphisms had significantly lower serum urate about 20–49, 21–51, and 18–54 μmol/l than non-minor-allele-genotypes.ConclusionsOur findings should be useful in identifying patients at risk for gout and high serum urate and these polymorphisms may be useful in personalized risk scores.Trial registrationPROSPERO registration number: CRD42018105275.
Highlights
Hyperuricemia, defined as serum urate > 7 mg/dl [1], can lead to gout [1] and increased risk of renal disease, diabetes, hypertension, and cardiovascular disease [2]
Many more individual studies have replicated the findings of Genome-wide association studies (GWAS) and these were summarized in systematic reviews of the effects of ATP-binding cassette sub-family G member 2 gene (ABCG2) [8,9,10,11,12,13] and Solute carrier family 2 member 9 (SLC2A9) [12, 14,15,16] polymorphisms on gout
The most recent review of SLC2A9 [15] included 13 studies indicating that rs6449213 (C versus T), rs16890979 (T versus C) and rs1014290 (C versus T) significantly decreased the risk of gout whereas rs3733591 increased the risk of gout only in Asian and Maori populations and Solomon Islanders
Summary
Hyperuricemia, defined as serum urate > 7 mg/dl (or 416.4 μmol/l) [1], can lead to gout [1] and increased risk of renal disease, diabetes, hypertension, and cardiovascular disease [2]. Genome-wide association studies (GWAS) have shown that many single nucleotide polymorphisms (SNPs) of ATP-binding cassette sub-family G member 2 gene (ABCG2) and the solute carrier family 2 member 9 (SLC2A9) are associated with serum urate and gout [3,4,5,6]. Both ABCG2 and SLC2A9 are located on chromosome 4 [7]. Replication studies showed conflicting effects of ABCG2 and SLC2A9 polymorphisms on gout and serum urate. This meta-analysis aimed to pool their effects across studies
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