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Common dysfunctional variants in ABCG2 are a major cause of early-onset gout.

ABSTRACT: Gout is a common disease which mostly occurs after middle age, but more people nowadays develop it before the age of thirty. We investigated whether common dysfunction of ABCG2, a high-capacity urate transporter which regulates serum uric acid levels, causes early-onset gout. 705 Japanese male gout cases with onset age data and 1,887 male controls were genotyped, and the ABCG2 functions which are estimated by its genotype combination were determined. The onset age was 6.5 years earlier with severe ABCG2 dysfunction than with normal ABCG2 function (P = 6.14 × 10(-3)). Patients with mild to severe ABCG2 dysfunction accounted for 88.2% of early-onset cases (twenties or younger). Severe ABCG2 dysfunction particularly increased the risk of early-onset gout (odds ratio 22.2, P = 4.66 × 10(-6)). Our finding that common dysfunction of ABCG2 is a major cause of early-onset gout will serve to improve earlier prevention and therapy for high-risk individuals.

SUBMITTER: Matsuo H

PROVIDER: S-EPMC3684804 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Common dysfunctional variants in ABCG2 are a major cause of early-onset gout.

Matsuo Hirotaka H Ichida Kimiyoshi K Takada Tappei T Nakayama Akiyoshi A Nakashima Hiroshi H Nakamura Takahiro T Kawamura Yusuke Y Takada Yuzo Y Yamamoto Ken K Inoue Hiroki H Oikawa Yuji Y Naito Mariko M Hishida Asahi A Wakai Kenji K Okada Chisa C Shimizu Seiko S Sakiyama Masayuki M Chiba Toshinori T Ogata Hiraku H Niwa Kazuki K Hosoyamada Makoto M Mori Atsuyoshi A Hamajima Nobuyuki N Suzuki Hiroshi H Kanai Yoshikatsu Y Sakurai Yutaka Y Hosoya Tatsuo T Shimizu Toru T Shinomiya Nariyoshi N

Scientific reports 20130101

Gout is a common disease which mostly occurs after middle age, but more people nowadays develop it before the age of thirty. We investigated whether common dysfunction of ABCG2, a high-capacity urate transporter which regulates serum uric acid levels, causes early-onset gout. 705 Japanese male gout cases with onset age data and 1,887 male controls were genotyped, and the ABCG2 functions which are estimated by its genotype combination were determined. The onset age was 6.5 years earlier with seve ...[more]

PMID: 23774753

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Project description:IntroductionGout is an inflammatory, metabolic disease associated with a high comorbidity burden including cardiovascular disease, hypertension, type 2 diabetes, hyperlipidemia, renal disease, and metabolic syndrome. Approximately 9.2 million Americans have gout, making prognosis and treatment outcome predictors highly important. About 600,000 Americans have early-onset gout (EOG), generally defined as first gout attack at ≤ 40 years of age. However, data on EOG clinical features, comorbidity profile, and treatment response are sparse; this systematic literature review provides insight.MethodsPubMed and American College of Rheumatology (ACR)/European Alliance of the Associations for Rheumatology (EULAR) abstract archives were searched for early-onset gout, "early onset gout," and ("gout" AND "age of onset"). Duplicate, foreign language, single case report, older (before 2016), and irrelevant/data insufficient publications were excluded. The age of diagnosis categorized patients as having common gout (CG, generally > 40 years) or EOG (generally ≤ 40 years). Applicable publications were extensively reviewed/discussed among authors for inclusion/exclusion consensus.ResultsA total of 283 publications were identified, with 46 (35 articles, 10 abstracts) reviewed and 17 (12 articles, 5 abstracts) ultimately included. Eleven reported clinical characteristics, with 6 EOG-CG retrospective/cross-sectional comparisons. Gout diagnosis preceded cardiometabolic comorbidity and renal comorbidities were less prevalent in EOG than CG patients. EOG patients had more severe disease (more gout flares, polyarticular disease), higher pre-therapy serum urate (SU), and worse oral urate-lowering therapy response. Genetics-focused publications reported higher incidences of dysfunctional urate transporter mutations in EOG patients.ConclusionsThis review suggests that EOG is more recalcitrant to urate-lowering therapy, is associated with urate transporter defects, and carries heavy disease burden. Therefore, early rheumatology referral and urate-lowering in a treat-to-target fashion may benefit EOG patients. Interestingly, EOG patients had fewer cardiometabolic comorbidities at diagnosis than CG patients, presenting a potential "window of opportunity" to attenuate cardiometabolic comorbidity development with SU control. Preventing gout-related suffering and health burden is particularly important in these young EOG patients who will live with gout and its sequelae for decades.

Dataset Information

Common dysfunctional variants in ABCG2 are a major cause of early-onset gout.

Publications

Common dysfunctional variants in ABCG2 are a major cause of early-onset gout.

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