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Zaidi, Faseeh; Narang, Ravi K; Phipps-Green, Amanda; Gamble, Greg G; Tausche, Anne-Katherin; So, Alexander; Riches, Philip; Andres, Mariano; Perez-Ruiz, Fernando; Doherty, Michael; Janssen, Matthijs; Joosten, Leo A B; Jansen, Tim L; Kurreeman, Fina; Torres, Rosa J; McCarthy, Geraldine M; Miner, Jeffrey N; Stamp, Lisa K; Merriman, Tony R; Dalbeth, Nicola

Systematic genetic analysis of early-onset gout: ABCG2 is the only associated locus

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  • Medientyp: E-Artikel
  • Titel: Systematic genetic analysis of early-onset gout: ABCG2 is the only associated locus
  • Beteiligte: Zaidi, Faseeh; Narang, Ravi K; Phipps-Green, Amanda; Gamble, Greg G; Tausche, Anne-Katherin; So, Alexander; Riches, Philip; Andres, Mariano; Perez-Ruiz, Fernando; Doherty, Michael; Janssen, Matthijs; Joosten, Leo A B; Jansen, Tim L; Kurreeman, Fina; Torres, Rosa J; McCarthy, Geraldine M; Miner, Jeffrey N; Stamp, Lisa K; Merriman, Tony R; Dalbeth, Nicola
  • Erschienen: Oxford University Press (OUP), 2020
  • Erschienen in: Rheumatology
  • Sprache: Englisch
  • DOI: 10.1093/rheumatology/kez685
  • ISSN: 1462-0324; 1462-0332
  • Schlagwörter: Pharmacology (medical) ; Rheumatology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Objective</jats:title> <jats:p>The aim of this study was to examine whether serum urate-associated genetic variants are associated with early-onset gout.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Participants with gout in the Genetics of Gout in Aotearoa study with available genotyping were included (n = 1648). Early-onset gout was defined as the first presentation of gout &amp;lt;40 years of age. Single nucleotide polymorphisms (SNPs) for the 10 loci most strongly associated with serum urate were genotyped. Allelic association of the SNPs with early-onset gout was tested using logistic regression in an unadjusted model and in a model adjusted for sex, body mass index, tophus presence, flare frequency, serum creatinine and highest serum urate. The analysis was also done in two replication cohorts: Eurogout (n = 704) and Ardea (n = 755), and data were meta-analysed.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>In the Genetics of Gout in Aotearoa study, there were 638 (42.4%) participants with early-onset gout. The ABCG2 rs2231142 gout risk T-allele was present more frequently in participants with early-onset gout compared with the later-onset group. For the other SNPs tested, no differences in risk allele number were observed. In the allelic association analysis, the ABCG2 rs2231142 T-allele was associated with early-onset gout in unadjusted and adjusted models. Analysis of the replication cohorts confirmed the association of early-onset gout with the ABCG2 rs2231142 T-allele, but not with other serum urate-associated SNPs. In the meta-analysis, the odds ratio (95% CI) for early-onset gout for the ABCG2 rs2231142 T-allele was 1.60 (1.41, 1.83).</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>In contrast to other serum urate-raising variants, the ABCG2 rs2231142 T-allele is strongly associated with early-onset gout.</jats:p> </jats:sec>
  • Zugangsstatus: Freier Zugang