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

被引：115

作者：

Matsuo, Hirotaka ^{[1
]}

Ichida, Kimiyoshi ^{[2
,3
]}

Takada, Tappei ^{[4
]}

Nakayama, Akiyoshi ^{[1
,5
]}

Nakashima, Hiroshi ^{[6
]}

Nakamura, Takahiro ^{[7
,8
]}

Kawamura, Yusuke ^{[1
]}

Takada, Yuzo ^{[9
]}

Yamamoto, Ken ^{[10
]}

Inoue, Hiroki ^{[1
]}

Oikawa, Yuji ^{[11
]}

Naito, Mariko ^{[12
]}

Hishida, Asahi ^{[12
]}

Wakai, Kenji ^{[12
]}

Okada, Chisa ^{[1
]}

Shimizu, Seiko ^{[1
]}

Sakiyama, Masayuki ^{[1
]}

Chiba, Toshinori ^{[1
]}

Ogata, Hiraku ^{[1
]}

Niwa, Kazuki ^{[11
]}

Hosoyamada, Makoto ^{[13
]}

Mori, Atsuyoshi ^{[14
]}

Hamajima, Nobuyuki ^{[15
]}

Suzuki, Hiroshi ^{[4
]}

Kanai, Yoshikatsu ^{[16
]}

Sakurai, Yutaka ^{[6
]}

Hosoya, Tatsuo ^{[3
]}

Shimizu, Toru ^{[17
]}

Shinomiya, Nariyoshi ^{[1
]}

机构：

[1] Natl Def Med Coll, Dept Integrat Physiol & Bionano Med, Tokorozawa, Saitama 3598513, Japan

[2] Tokyo Univ Pharm & Life Sci, Dept Pathophysiol, Hachioji, Tokyo 1920392, Japan

[3] Jikei Univ, Sch Med, Dept Internal Med, Div Kidney & Hypertens,Minato Ku, Tokyo 1058471, Japan

[4] Univ Tokyo, Fac Med, Tokyo Univ Hosp, Dept Pharm,Bunkyo Ku, Tokyo 1138655, Japan

[5] Japan Air Self Def Force, Iwo To Air Base Grp, Med Grp, Ogasawara, Tokyo 1002100, Japan

[6] Natl Def Med Coll, Dept Prevent Med & Publ Hlth, Tokorozawa, Saitama 3598513, Japan

[7] Natl Def Med Coll, Premed Course, Lab Math, Tokorozawa, Saitama 3598513, Japan

[8] Inst Phys & Chem Res RIKEN, Ctr Genom Med, Lab Stat Anal, Minato Ku, Tokyo 1088639, Japan

[9] Natl Def Med Coll, Cent Res Inst, Lab Biofunct, Tokorozawa, Saitama 3598513, Japan

[10] Kyushu Univ, Med Inst Bioregulat, Res Ctr Genet Informat, Div Genome Anal,Higashi Ku, Fukuoka 8128582, Japan

[11] Toho Univ, Fac Sci, Dept Biol, Funabashi, Chiba 2748510, Japan

[12] Nagoya Univ, Grad Sch Med, Dept Prevent Med, Showa Ku, Nagoya, Aichi 4668550, Japan

[13] Teikyo Univ, Sch Pharmaceut Sci, Dept Human Physiol & Pathol, Itabashi Ku, Tokyo 1738605, Japan

[14] Seirei Prevent Hlth Care Ctr, Hamamatsu, Shizuoka 4338558, Japan

[15] Nagoya Univ, Grad Sch Med, Young Leaders Program, Dept Healthcare Adm,Showa Ku, Nagoya, Aichi 4668550, Japan

[16] Osaka Univ, Grad Sch Med, Dept Pharmacol, Div Biosyst Pharmacol, Suita, Osaka 5650871, Japan

[17] Midorigaoka Hosp, Takatsuki, Osaka 5691121, Japan

来源：

SCIENTIFIC REPORTS | 2013年 / 3卷

基金：

日本学术振兴会;

关键词：

GENOME-WIDE ASSOCIATION; URIC-ACID; GENE; SUSCEPTIBILITY; LINKAGE; RISK; IDENTIFICATION; HYPERURICEMIA; ARTHRITIS; INSIGHTS;

D O I：

10.1038/srep02014

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 x 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 x 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.

引用

页数：4

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