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Sci Rep. 2014 Jun 9;4:5227. doi: 10.1038/srep05227.

Common dysfunctional variants of ABCG2 have stronger impact on hyperuricemia progression than typical environmental risk factors.

Author information

1
1] Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan [2] Medical Group, Headquarters, Iwo-to Air Base Group, Japan Air Self-Defense Force, Iwo-to, Ogasawara, Tokyo 100-2100, Japan [3].
2
1] Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan [2].
3
Division of Human Genetics, Department of Integrated Genetics, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-0801, Japan.
4
1] Laboratory for Mathematics, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan [2] Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Core for Genomic Medicine, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
5
Department of Preventive Medicine and Public Health, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
6
The Central Research Institute, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
7
Department of Laboratory Medicine, Toho University Ohashi Medical Center, 2-17-6 Ohashi, Meguro-ku, Tokyo 153-8515, Japan.
8
Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
9
Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
10
Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
11
1] Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, 3-19-18 Shinbashi, Minato-ku, Tokyo 105-8471, Japan [2] Department of Pathophysiology and Therapy in Chronic Kidney Disease, Jikei University School of Medicine, 3-19-18 Shinbashi, Minato-ku, Tokyo 105-8471, Japan.
12
1] Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, 3-19-18 Shinbashi, Minato-ku, Tokyo 105-8471, Japan [2] Department of Pathophysiology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachiouji, Tokyo 192-0392, Japan.

Abstract

Gout/hyperuricemia is a common multifactorial disease having typical environmental risks. Recently, common dysfunctional variants of ABCG2, a urate exporter gene also known as BCRP, are revealed to be a major cause of gout/hyperuricemia. Here, we compared the influence of ABCG2 dysfunction on serum uric acid (SUA) levels with other typical risk factors in a cohort of 5,005 Japanese participants. ABCG2 dysfunction was observed in 53.3% of the population investigated, and its population-attributable risk percent (PAR%) for hyperuricemia was 29.2%, much higher than those of the other typical environmental risks, i.e. overweight/obesity (BMI ≥ 25.0; PAR% = 18.7%), heavy drinking (>196 g/week (male) or >98 g/week (female) of pure alcohol; PAR% = 15.4%), and aging (≥60 years old; PAR% = 5.74%). SUA significantly increased as the ABCG2 function decreased (P = 5.99 × 10(-19)). A regression analysis revealed that ABCG2 dysfunction had a stronger effect than other factors; a 25% decrease in ABCG2 function was equivalent to "an increase of BMI by 1.97-point" or "552.1 g/week alcohol intake as pure ethanol" in terms of ability to increase SUA. Therefore, ABCG2 dysfunction originating from common genetic variants has a much stronger impact on the progression of hyperuricemia than other familiar risks. Our study provides a better understanding of common genetic factors for common diseases.

PMID:
24909660
PMCID:
PMC5381477
DOI:
10.1038/srep05227
[Indexed for MEDLINE]
Free PMC Article

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