Dataset Information

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??mol/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??mol/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 .

SUBMITTER: Lukkunaprasit T

PROVIDER: S-EPMC7580000 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Lukkunaprasit Thitiya T Rattanasiri Sasivimol S Turongkaravee Saowalak S Suvannang Naravut N Ingsathit Atiporn A Attia John J Thakkinstian Ammarin A

BMC medical genetics 20201021 1

<h4>Background</h4>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.<h4>Methods</h4>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 independe ...[more]

PMID: 33087043

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Project description:BackgroundOsteoarthritis of the knee is an irreversible disease that causes great pain, and genetic factors play an important role in its occurrence and development. There have been many studies on the correlation between ADAM12 polymorphisms and genetic susceptibility to osteoarthritis, but the results remain inconclusive.MethodsPapers from PubMed, Web of Science, EMbase, Springer, SCOPUS, Google Scholar and other databases were systematically retrieved with a cut-off of January 2022. All case-control studies on ADAM12 rs3740199, rs1871054, rs1044122, and rs1278279 polymorphisms and osteoarthritis were searched. Fixed or random effects models were used for pooled analysis with OR values and 95% confidence intervals (CI), and publication bias was assessed. In addition, the false-positive reporting probability test was used to assess the confidence of a statistically significant association.ResultsEleven articles were included, which included 3332 patients with osteoarthritis and 5108 healthy controls. Meta-analysis showed that the rs1871054 polymorphism of ADAM12 was associated with osteoarthritis in dominant, recessive, allelic, and homozygote genetic models [C vs. T: OR = 1.34 95% CI (1.05, 1.71), P < 0.001]. Our subgroup analysis revealed an association between the ADAM12 polymorphism rs1871054 in Asians and osteoarthritis [C vs. T: OR = 1.61, 95% CI (1.25, 2.08), P < 0.001], albeit this was only for three studies. In addition, the ADAM12 polymorphism rs1871054 is associated with osteoarthritis in patients younger than 60 years of age [C vs. T: OR = 1.39, 95% CI (1.01, 1.92), P = 0.289]; however, the ADAM12 gene rs3740199, rs1044122, and rs1278279 site polymorphisms were not significantly. Furthermore, when assessing the confidence of the positive results, the positive results were found to be credible (except for Age < 60).ConclusionPolymorphism at the rs1871054 site of ADAM12 is associated with genetic susceptibility to osteoarthritis, but rs3740199, rs1044122, and rs1278279 site polymorphisms are not.

Project description:Background: Numerous studies have demonstrated an association between osteoprotegerin (OPG) polymorphisms (A163G (rs3102735), T245G (rs3134069), T950C (rs2073617), G1181C (rs2073618)) and osteoporosis risk. However, their conclusions are inconsistent. In addition, some new studies have been updated, and more importantly, previous meta-analyses have not tested for false-positive results. In order to further explore these associations, we recently conducted a meta-analysis. Objectives: To study the relationship between OPG polymorphisms A163G, T245G, T950C, G1181C and the risk of osteoporosis. Methods: PubMed, Medline, International Statistical Institute (ISI), China National Knowledge Infrastructure (CNKI) and China Wanfang Database were used for research searches. Associations were assessed with five genetic models using odds ratios (ORs) with 95% confidence intervals (CIs). In addition, confidence in statistically significant associations was assessed using false-positive report probability (FPRP), Bayesian probability of False discovery (BFDP), and Venice criteria. Results: On the whole, the OPG A163G polymorphism was not significantly associated with risk of osteoporosis. However, in a subgroup analysis, we found that the OPG A163G polymorphism increased the risk of osteoporosis in Caucasians (AG + GG vs AA: OR = 1.35, 95% CI = 1.06-1.73; AA + GG vs AG: OR = 0.64, 95% CI = 0.49-0.82) and the female (G vs A: OR = 1.30, 95% CI = 1.03-1.64; AG + GG vs AA: OR = 1.42, 95% CI = 1.18-1.71). At the same time, the OPG G1181C polymorphism reduces the risk of osteoporosis (C vs G: OR = 0.84, 95% CI = 0.74-0.95; CC vs GG: OR = 0.75, 95% CI = 0.60-0.93; GC + CC vs GG: OR = 0.80, 95% CI = 0.67-0.95; CC vs GG + GC: OR = 0.84, 95% CI = 0.70-1.00). Moreover, a significantly decreased risk of osteoporosis was also discovered in Asian (C vs G: OR = 0.80, 95% CI = 0.66-0.98; CC vs GG: OR = 0.67, 95% CI = 0.47-0.95; GC + CC vs GG: OR = 0.74, 95% CI = 0.58-0.95) and the female (C vs G: OR = 0.85, 95% CI = 0.75-0.97; CC vs GG: OR = 0.77, 95% CI = 0.61-0.96; GC + CC vs GG: OR = 0.79, 95% CI = 0.66-0.95). Finally, we did not find a close association between OPG T245G and T950C polymorphisms and osteoporosis risk. However, when we retained only studies in the control group that was consistent with Hardy-Weinberg equilibrium (HWE) and high-quality scores, we observed that the OPG A163G polymorphism increased the risk of osteoporosis in the overall analysis (G vs A: OR = 1.40, 95% CI = 1.16-1.68; GG vs AA: OR = 1.96, 95% CI = 1.20-3.21; AG + GG vs AA: OR = 1.45, 95% CI = 1.22-1.72). Finally, after the credibility assessment, we concluded that all statistically significant association results in the meta-analysis in this study and those in the previous study were 'positive results with low confidence'. Conclusion: In conclusion, our study concluded that all meaningful results between OPG A163G and G1181C polymorphisms and osteoporosis risk were false-positive results rather than true associations.

Dataset Information

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

Publications

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

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