Background Replication 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. Methods Studies 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. Results Fifty-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. Conclusions Our 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 registration PROSPERO registration number: CRD42018105275.
This meta-analysis was conducted to determine the genotypic effects of rs4149056 and rs2306283 polymorphism in SLCO1B1 gene on myopathy in patients with statin. Studies were searched using multiple databases and selected following inclusion criteria. Two reviewers independently performed data extraction and assessments for risk of bias. Fixed-or-random-effect was applied to pool allele frequency/effects. Mixed-effect logit model was used to pool genotypic effects using individual patient data. Heterogeneity and publication bias were explored. Fourteen studies were pooled for rs4149056; the minor C allele frequency were 15% in Caucasians and 14% in Asians. Six studies were pooled for rs2306283; the minor G allele frequency was 34% in Caucasian and 75% in Asians. Genotypic effects of rs4149056 polymorphism in Caucasians indicated that statin users who carried CC and TC genotypes had a significantly higher risk of myopathy than those who carried TT genotype, with a pooled odds ratio (OR) of 2.9 (95% confidence interval, 1.59, 5.34) and 1.6 (1.20, 2.16), respectively. For subgroup analysis, CC and TC genotypes also suggested a higher risk of myopathy in simvastatin users [OR = 2.8 (1.17, 6.77) and OR = 1.8 (1.15, 2.77), respectively] and in atorvastatin users [OR = 4.0 (1.23, 12.63) and OR = 2.0 (1.11, 3.52), respectively] than those who carried TT genotype. There was no significant association between rs2306283 polymorphism and myopathy in Caucasians and Asians. There was no evidence of publication bias for both polymorphisms.
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