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.

Metagenome-genome-wide association studies reveal human genetic impact on the oral microbiome

“…3c ; p discovery = 4.69 × 10 −9 ; p replication = 0.04) . SLC2A9 is a urate transporter and SLC2A9 polymorphisms have been reported associated with serum uric acid and urine uric acid concentration in multiple studies 27 – 29 . We also looked at these top loci in Biobank Japan (BBJ) 30 , 31 , and SLC2A9 was correlated with lower serum uric acid concentration (Supplementary Fig.…”

The Role of ABCG2 in the Pathogenesis of Primary Hyperuricemia and Gout—An Update

“…Hyperuricemia and gout pathology has often been shown to be related to genetic predisposition [30] and to be affected by SNPs in many of the genes encoding urate transporters [87,88]. Among these, especially SNPs of ABCG2 have been highly associated with pediatric-onset hyperuricemia and early-onset gout [89][90][91][92][93].…”

Prevalence and potential relevance of hyperuricemia in pediatric kidney transplant recipients—a CERTAIN registry analysis

“…On the other hand, the strengths of this study are its size (so far the largest pediatric KTx cohort in which serum uric acid concentrations was studied) and its multicenter design, which increases the generalizability of the data and reduces the confounding effect of genetic predisposition to hyperuricemia existing in certain populations. 64,65 In conclusion, we observed a high prevalence (43%) of hyperuricemia in pediatric KTx recipients sometime posttransplant and an association of serum uric acid levels with a more pronounced decline of eGFR. Systolic blood pressure tended to be higher in patients with severe hyperuricemia.…”

“…Furthermore, the size of the study population did not allow us to assess by multivariable analysis whether the association of serum uric acid concentrations with the decline of eGFR was independent of other factors such as rejection, infections or donor‐specific antibodies. On the other hand, the strengths of this study are its size (so far the largest pediatric KTx cohort in which serum uric acid concentrations was studied) and its multicenter design, which increases the generalizability of the data and reduces the confounding effect of genetic predisposition to hyperuricemia existing in certain populations 64,65 …”