Identification and analysis of genes influencing serum uric acid levels

结合无功能SNP Q126X和半功能SNP Q141K对尿酸排泄转运蛋白ABCG2的功能进行了评价。估计的ABCG2功能障碍导致尿尿酸排泄增加，这一机制在ABCG2基因敲除小鼠中被阐明。作为高尿酸血症的一种新机制，我们证明了高尿酸血症是由于ABCG2引起肠尿酸排泄减少，导致尿尿酸排泄增加(肾外尿酸排泄型高尿酸血症)。我们还指出，ABCG2功能障碍与早发性痛风有关，轻度和轻度功能障碍主要导致排泄型高尿酸血症，而严重功能障碍则导致肾外尿酸盐排泄型高尿酸血症。

A function of ABCG2, urate excretive transporter, is evaluated by the combination of the no-functional SNP, Q126X and the half functional SNP, Q141K. The estimated ABCG2 dysfunction leads to the urinary urate excretion increase and this mechanism was elucidated using Abcg2 knock-out mice. As a new mechanism for hyperuricemia, we demonstrated that hyperuricemia results from the intestinal urate excretion decrease via ABCG2, leading to urinary urate excretion increase (extra-renal urate underexcretion type hyperuricemia). We also indicated that ABCG2 dysfunction is related with early-onset gout and that the slight and mild dysfunctions mainly cause underexcretion type hyperuricemia, while severe dysfunction causes extra-renal urate underexcretion type hyperuricemia.