ABCG2 DYSFUNCTION INCREASES THE RISK OF RENAL OVERLOAD HYPERURICEMIA

被引：66

作者：

Matsuo, Hirotaka ^{[1
]}

Takada, Tappei ^{[2
]}

Nakayama, Akiyoshi ^{[1
]}

Shimizu, Toru ^{[3
]}

Sakiyama, Masayuki ^{[1
]}

Shimizu, Seiko ^{[1
]}

Chiba, Toshinori ^{[1
]}

Nakashima, Hiroshi ^{[4
]}

Nakamura, Takahiro ^{[5
]}

Takada, Yuzo ^{[6
]}

Sakurai, Yutaka ^{[4
]}

Hosoya, Tatsuo ^{[7
]}

Shinomiya, Nariyoshi ^{[1
]}

Ichida, Kimiyoshi ^{[7
,8
]}

机构：

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

[2] Univ Tokyo, Fac Med, Tokyo Univ Hosp, Dept Pharm, Tokyo 113, Japan

[3] Midorigaoka Hosp, Takatsuki, Osaka, Japan

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

[5] Natl Def Med Coll, Lab Math, Tokorozawa, Saitama 3598513, Japan

[6] Natl Def Med Coll, Cent Res Inst, Tokorozawa, Saitama 3598513, Japan

[7] Jikei Univ, Sch Med, Dept Internal Med, Div Kidney & Hypertens, Tokyo, Japan

[8] Tokyo Univ Pharm & Life Sci, Dept Pathophysiol, Tokyo, Japan

来源：

NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS | 2014年 / 33卷 / 4-6期

关键词：

ABC transporters; hyperuricemia/gout; renal urate overload; extra-renal underexcretion type; RESISTANCE PROTEIN TRANSPORTER; GOUT; IDENTIFICATION; CLASSIFICATION;

D O I：

10.1080/15257770.2013.866679

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

ATP-binding cassette transporter, sub-family G, member 2 (ABCG2/BCRP) is identified as a high-capacity urate exporter, and its dysfunction has an association with serum uric acid levels and gout/hyperuricemia risk. Generally, hyperuricemia has been classified into urate "overproduction type," "underexcretion type," and "combined type" based on only renal urate excretion, without considering an extra-renal pathway such as gut excretion. In this study, we investigated the effects of ABCG2 dysfunction on human urate handling and the mechanism of hyperuricemia. Clinical parameters for urate handling including urinary urate excretion (UUE) were examined in 644 Japanese male outpatients with hyperuricemia. The severity of their ABCG2 dysfunction was estimated by genotype combination of two common ABCG2 variants, nonfunctional Q126X (rs72552713) and half-functional Q141K (rs2231142). Contrary to the general understanding that ABCG2 dysfunction leads to decreased renal urate excretion, UUE was significantly increased by ABCG2 dysfunction (P = 3.60 x 10(-10)). Mild, moderate, and severe ABCG2 dysfunctions significantly raised the risk of "overproduction" hyperuricemia including overproduction type and combined type, conferring risk ratios of 1.36, 1.66, and 2.35, respectively. The present results suggest that common dysfunctional variants of ABCG2 decrease extra-renal urate excretion including gut excretion and cause hyperuricemia. Thus, "overproduction type" in the current concept of hyperuricemia should be renamed "renal overload type," which is caused by two different mechanisms, "extra-renal urate underexcretion" and genuine "urate overproduction." Our new concept will lead to a more accurate diagnosis and more effective therapeutic strategy for hyperuricemia and gout.

引用

页码：266 / 274

页数：9

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