Systematic genetic analysis of early-onset gout: ABCG2 is the only associated locus
Objective. The aim of this study was to examine whether serum urate-associated genetic variants are associated with early-onset gout. Methods. 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 firs...
| Autores: | , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL) |
| Repositorio: | r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante |
| OAI Identifier: | oai:isabial.fundanetsuite.com:p6627 |
| Acceso en línea: | https://isabial.portalinvestigacion.com/publicaciones6627 https://academic.oup.com/rheumatology/article/59/9/2544/5717950?login=true |
| Access Level: | acceso abierto |
| Palabra clave: | gout genetics urate |
| Sumario: | Objective. The aim of this study was to examine whether serum urate-associated genetic variants are associated with early-onset gout. Methods. 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 <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. Results. 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). Conclusion. In contrast to other serum urate-raising variants, the ABCG2 rs2231142 T-allele is strongly associated with early-onset gout. |
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