Association of a common nonsynonymous variant in GLUT9 with serum uric acid levels in old order amish.
Association of a common nonsynonymous variant in GLUT9 with serum uric acid levels in old order amish.
复制标题
GLUT9中常见非同义变体与旧顺序Amish的血清尿酸水平的关联。
DOI：
10.1002/art.23752
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发表时间：
2008-09
影响因子：
--
通讯作者：
Shuldiner, Alan R.
中科院分区：
文献类型：
--
作者：
McArdle, Patrick F.;Parsa, Afishin;Chang, Yen-Pei C.;Weir, Matthew R.;O'Connell, Jeffery R.;Mitchell, Braxton D.;Shuldiner, Alan R.
尿酸是嘌呤代谢的主要终产物。血清尿酸升高与痛风性关节炎以及多种心血管相关表型有关。在来自宾夕法尼亚州兰开斯特县的一组旧秩序阿米什人中进行血清尿酸水平的500，000 SNP全基因组关联研究。扫描证实了先前在4号染色体上发现的区域与尿酸水平密切相关（rs 10489070的p = 4.2×10−11）。随访基因分型显示GLUT 9中的非同义编码SNP（Val 253 Ile; rs 16890979）与尿酸水平最密切相关，每个拷贝的次要等位基因与0.47 mg/dl的尿酸减少相关（95%置信区间：0.31 − 0.63; p = 1.43 × 10−11）。这种变异的影响在女性中往往比男性更强（性别×基因型相互作用p = 0.16）。基因型效应并没有因为纳入了几个心血管危险因素而改变，这表明GLUT 9与尿酸稳态直接相关。在阿米什人全基因组扫描中鉴定的相同SNP（rs 10489070）与Frachial Heart研究中的痛风显著相关（p = 0.004）。我们的结论是，GLUT 9，这是在肾脏中表达的可能是一种新的调节尿酸消除和一个常见的非同义变异，在这个基因有助于异常尿酸稳态和痛风。
Uric acid is the primary end product of purine metabolism. Increased serum uric acid has been associated with gouty arthritis as well as with a variety of cardiovascular related phenotypes. A 500,000 SNP genome wide association study of serum uric acid levels was performed in a cohort of Old Order Amish from Lancaster County, Pennsylvania. The scan confirmed a previously identified region on chromosome 4 to be strongly associated with uric acid levels (p = 4.2×10−11 for rs10489070). Follow-up genotyping revealed a non-synonymous coding SNP (Val253Ile; rs16890979) in GLUT9 that was most strongly associated with uric acid levels, with each copy of the minor allele associated with 0.47 mg/dl less uric acid (95% confidence interval: 0.31 − 0.63; p = 1.43 × 10−11). The effect of this variant tended to be stronger in women than in men (p = 0.16 for sex × genotype interaction). The genotypic effect was not modified by the inclusion of several cardiovascular risk factors suggesting that GLUT9 is directly related to uric acid homeostasis. The same SNP (rs10489070) identified in the Amish genome wide scan was significantly associated with gout in the Framingham Heart Study (p = 0.004). We conclude that GLUT9, which is expressed in the kidney may be a novel regulator of uric acid elimination and a common non-synonymous variant in this gene contributes to abnormalities in uric acid homeostasis and gout.
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