The association between genetic polymorphisms in ABCG2 and SLC2A9 and urate: an updated systematic review and meta-analysis

Abstract

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 .

Keywords: ABCG2; Gout; Hyperuricemia; Meta-analysis; SLC2A9; Single nucleotide polymorphism; Urate.

Fig. 1

Flow for identifying and selecting studies. ABCG2, ATP-binding cassette sub-family G member 2; SLC2A9, solute carrier family 2 member 9

Fig. 2

Summary of pooled genotype effects on gout. a Increasing risk effects b Decreasing risk effects. ABCG2, ATP-binding cassette sub-family G member 2; CI, confidence interval; OR, odds ratio; SLC2A9, solute carrier family 2 member 9; SNP, single nucleotide polymorphism

Fig. 3

Summary of pooled genotype risk effects on hyperuricemia. ABCG2, ATP-binding cassette sub-family G member 2; CI, confidence interval; OR, odds ratio; SNP, single nucleotide polymorphism

Fig. 4

Summary of pooled genotype effects on mean difference of serum urate. a Increasing risk effects b Decreasing risk effects. ABCG2, ATP-binding cassette sub-family G member 2; CI, confidence interval; MD, mean difference; SLC2A9, solute carrier family 2 member 9; SNP, single nucleotide polymorphism