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

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.

• Authors: Akiyoshi Nakayama, Hirotaka Matsuo, Hirofumi Nakaoka, Takahiro Nakamura, Hiroshi Nakashima, Yuzo Takada, Yuji Oikawa, Tappei Takada, Masayuki Sakiyama, Seiko Shimizu, Yusuke Kawamura, Toshinori Chiba, Junko Abe, Kenji Wakai, Sayo Kawai, Rieko Okada, Takashi Tamura, Yuka Shichijo, Airi Akashi, Hiroshi Suzuki, Tatsuo Hosoya, Yutaka Sakurai, Kimiyoshi Ichida, Nariyoshi Shinomiya
• Journal: Scientific reports (Sci Rep) Vol. 4 Pg. 5227 (Jun 09 2014) ISSN: 2045-2322 [Electronic] England
• PMID: 24909660 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ABCG2 protein, human
• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters
• Neoplasm Proteins
• Uric Acid

Topics

• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters (genetics)
• Asian People (genetics)
• Cohort Studies
• Disease Progression
• Female
• Genetic Predisposition to Disease (genetics)
• Genetic Variation (genetics)
• Gout (blood, genetics)
• Humans
• Hyperuricemia (blood, genetics, pathology)
• Male
• Middle Aged
• Neoplasm Proteins (genetics)
• Risk Factors
• Uric Acid (blood)