A major risk of early-onset gout: ABCG2 dysfunction in a Japanese male population

Nakayama, Akiyoshi

A major risk of early-onset gout: ABCG2 dysfunction in a Japanese male population

Sunday, 17 August 2014

Exhibit hall (Dena'ina Center)

Akiyoshi Nakayama, MD , National Defense Medical College, Tokorozawa, Japan

Hirotaka Matsuo, PhD , National Defense Medical College, Tokorozawa, Japan

Kimiyoshi Ichida, PhD , Tokyo University of Pharmacy and Life Sciences, Hachiouji, Japan

Tappei Takada, PhD , the University of Tokyo Hospital, Bunkyo-ku, Japan

Hiroshi Nakashima, PhD , National Defense Medical College, Tokorozawa, Japan

Takahiro Nakamura, PhD , National Defense Medical College, Tokorozawa, Japan

Yuzo Takada, PhD , National Defense Medical College, Tokorozawa, Japan

Seiko Shimizu, PhD , National Defense Medical College, Tokorozawa, Japan

Masayuki Sakiyama, MD , National Defense Medical College, Tokorozawa, Japan

Nobuyuki Hamajima, PhD , Nagoya University Graduate School of Medicine, Nagoya, Japan

Yutaka Sakurai, PhD , National Defense Medical College, Tokorozawa, Japan

Toru Shimizu, PhD , Midorigaoka Hospital, Takatsuki, Japan

Nariyoshi Shinomiya, PhD , National Defense Medical College, Tokorozawa, Japan

INTRODUCTION:

Gout is a common disease which many people in their middle age and elder suffer from, but nowadays the number of young patients is increasing. ATP-binging cassette (ABC) transporter, subfamily G, member 2 (ABCG2/BCRP) is a high-capacity urate exporter which regulates serum uric acid levels. ABCG2 is known for a major genetic cause of gout, but relationship with early-onset gout is still unrevealed. We then conducted a study to examine whether ABCG2 dysfunction causes early-onset gout

METHODS:

ABCG2 functions were estimated from their genotype combinations of Q126X (rs72552713) and Q141K (rs2231142) in ABCG2. ABCG2 transport functions are then divided into four groups, full function, 3/4 function (mild dysfunction), 1/2 function (moderate dysfunction), and ≤1/4 function (severe dysfunction). We genotyped 2,593 Japanese male (706 clinically-diagnosed gout cases with onset age data and 1,887 controls) to estimate their ABCG2 functions and conducted a logistic regression analysis among them by SPSS v.16.0J and JMP10.0.0.

RESULTS:

The mean onset age was 6.5 years earlier for those with severe ABCG2 dysfunction than those with normal ABCG2 function (P=6.14×10^-3). Patients with any dysfunctional ABCG2 accounted for 88.2% of early-onset cases (onset age < 30 years old). Any dysfunctional ABCG2 show significant risks of early-onset gout. Especially, in severe ABCG2 dysfunction, the risk of early-onset gout reaches the odds ratio of 22.2 (95% CI 5.89-83.7, P = 4.66×10^-6).

CONCLUSIONS:

We showed that common dysfunctional variants of ABCG2 are the major risk of early-onset gout. Therefore, early screening of ABCG2 dysfunction by genotyping and appropriate interventions will provide great benefit for high-risk individuals and make a substantial contribution for public health.