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.

Figure 1. Onset age of gout for each ABCG2 function.

The onset age of cases with 1/4 function or less was 38.2 years old, whereas that with full function was 44.7 years old, a difference of 6.5 years. All bars show mean ± s.e.m.

Figure 2. Odds ratios for ABCG2 dysfunctions among gout patients in each onset age group.

Shown are the odds ratios (ORs) on a log₁₀ scale of the gout risks for each onset age group and ABCG2 dysfunction. ORs and 95% confidence intervals (CIs) for each ABCG2 dysfunction were obtained by comparing with full function and adjusted for body mass index with logistic regression analysis. Circles and diamonds with horizontal lines indicate ORs with 95% CIs of each onset age groups. All ABCG2 dysfunction levels significantly increased the risk of gout (OR > 2.38) in all onset-age groups. Severe ABCG2 dysfunction especially increased the risk of early-onset gout, conferring an adjusted OR of 22.2.