Common dysfunctional variants of ABCG2 have stronger impact on hyperuricemia progression than typical environmental risk factors.
Common dysfunctional variants of ABCG2 have stronger impact on hyperuricemia progression than typical environmental risk factors.
复制标题
ABCG2 的常见功能失调变异对高尿酸血症进展的影响比典型的环境危险因素更强。
DOI：
10.1038/srep05227
复制
发表时间：
2014-06-09
影响因子：
4.6
通讯作者：
Shinomiya N
中科院分区：
文献类型：
--
作者：
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;Ichida K;Shinomiya N
痛风/高尿酸血症是一种常见的多因素疾病，具有典型的环境风险。最近，ABCG 2（一种尿酸盐输出基因，也称为BCRP）的常见功能障碍变体被发现是痛风/高尿酸血症的主要原因。在这里，我们比较了ABCG 2功能障碍对血清尿酸（SUA）水平的影响与其他典型的危险因素，在一个队列的5,005名日本参与者。ABCG 2功能障碍在53.3%的调查人群中观察到，其高尿酸血症的人群归因风险百分比（PAR%）为29.2%，远高于其他典型环境风险，即超重/肥胖（BMI ≥ 25.0; PAR% = 18.7%），大量饮酒（纯酒精>196 g/周（男性）或>98 g/周（女性）; PAR% = 15.4%）和衰老（≥60岁; PAR% = 5.74%）。 随着ABCG 2功能的下降，SUA显著增加（P = 5.99 × 10−19）。回归分析显示，ABCG 2功能障碍的影响比其他因素更强;就增加SUA的能力而言，ABCG 2功能降低25%相当于“BMI增加1.97点”或“552.1 g/周纯乙醇酒精摄入量”。 因此，源自常见遗传变异的ABCG 2功能障碍对高尿酸血症进展的影响比其他常见风险更大。我们的研究提供了对常见疾病的常见遗传因素的更好理解。
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.