Faseeh Zaidi1, Ravi K Narang1, Amanda Phipps-Green2, Greg G Gamble1, Anne-Katherin Tausche3, Alexander So4, Philip Riches5, Mariano Andres6, Fernando Perez-Ruiz7, Michael Doherty8, Matthijs Janssen9, Leo A B Joosten10,11, Tim L Jansen9, Fina Kurreeman12, Rosa J Torres13,14, Geraldine M McCarthy15, Jeffrey N Miner16, Lisa K Stamp17, Tony R Merriman2, Nicola Dalbeth1. 1. Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, AucklandNew Zealand. 2. Department of Biochemistry, University of Otago, Dunedin, New Zealand. 3. Department of Rheumatology, Technical University Dresden, Dresden, Germany. 4. Department of Medicine, Service of Rheumatology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland. 5. Rheumatology and Bone Disease Unit, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. 6. Department of Medicine, Sección de Reumatología, Hospital General Universitario de Alicante, Alicante, Spain. 7. Rheumatology Division, Hospital Universitario Cruces, Baracaldo, Biscay, Spain. 8. Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham, Nottingham, UK. 9. Department of Rheumatology, VieCuri Medical Center, Venlo, The Netherlands. 10. Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. 11. Department of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania. 12. Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. 13. Department of Biochemistry, La Paz University Hospital Health Research Institute (FIBHULP), IdiPaz, Madrid, Spain. 14. Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain. 15. Department of Rheumatology, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland. 16. Ardea Biosciences, Inc., San Diego, CA, USA. 17. Department of Medicine, University of Otago, Christchurch, New Zealand.
Abstract
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.
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 ABCG2rs2231142gout 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 ABCG2rs2231142 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 ABCG2rs2231142 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 ABCG2rs2231142 T-allele was 1.60 (1.41, 1.83). CONCLUSION: In contrast to other serum urate-raising variants, the ABCG2rs2231142 T-allele is strongly associated with early-onset gout.
Authors: Youssef M Roman; Donna McClish; Elvin T Price; Roy T Sabo; Owen M Woodward; Tesfaye B Mersha; Nehal Shah; Andrew Armada; Robert Terkeltaub Journal: Am Heart J Plus Date: 2022-04-27
Authors: Rebekah Wrigley; Amanda J Phipps-Green; Ruth K Topless; Tanya J Major; Murray Cadzow; Philip Riches; Anne-Kathrin Tausche; Matthijs Janssen; Leo A B Joosten; Tim L Jansen; Alexander So; Jennie Harré Hindmarsh; Lisa K Stamp; Nicola Dalbeth; Tony R Merriman Journal: Arthritis Res Ther Date: 2020-03-12 Impact factor: 5.156
Authors: Young Sun Suh; Hae Sook Noh; Hyun-Jin Kim; Yun-Hong Cheon; Mingyo Kim; Hanna Lee; Hyun-Ok Kim; Sang-Il Lee Journal: Metabolites Date: 2021-06-18