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.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Nakayama A,Matsuo H,Nakaoka H,Nakamura T,Nakashima H,Takada Y,Oikawa Y,Takada T,Sakiyama M,Shimizu S,Kawamura Y,Chiba T,Abe J,Wakai K,Kawai S,Okada R,Tamura T,Shichijo Y,Akashi A,Suzuki H,Hosoya T,Sakurai Y,Icdoi
10.1038/srep05227subject
Has Abstractpub_date
2014-06-09 00:00:00pages
5227issn
2045-2322pii
srep05227journal_volume
4pub_type
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