SLC2A9 influences uric acid concentrations with pronounced sex-specific effects
SLC2A9 influences uric acid concentrations with pronounced sex-specific effects
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DOI：
10.1038/ng.107
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发表时间：
2008-04-01
期刊：
影响因子：
30.8
通讯作者：
Meisinger, Christa
中科院分区：
文献类型：
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作者：
Doering, Angela;Gieger, Christian;Meisinger, Christa
血清尿酸浓度与痛风和心血管疾病和糖尿病等临床实体相关。在全基因组关联研究KORA（Kooperative Gesundheitsforschung in der Region Augsburg）F3 500 K（n = 1，644）中，与尿酸浓度相关的最显著SNP定位在SLC 2A 9的内含子4和6内，SLC 2A 9是一种编码推定的己糖转运蛋白的基因（效应：每拷贝次要等位基因-0.23至-0.36 mg/dl）。我们在来自德国（KORA S4和SHIP（波美拉尼亚健康研究））和奥地利（SAPHIR;高个体风险受试者的萨尔茨堡动脉粥样硬化预防计划）的三个独立样本中复制了这些发现，P值范围为1.2 x 10（-8）至1.0 x 10（-32）。KORA F3 500 K亚组（n = 117）的全血RNA表达谱分析显示，SLC 2A 9亚型2与尿酸盐浓度之间存在显著相关性。SLC 2A 9基因型也显示与自我报告的痛风显著相关。基因型解释的血清尿酸浓度变异的比例在男性中约为1.2%，在女性中约为6%，表达水平解释的比例在男性中约为3.5%，在女性中约为15%。
Serum uric acid concentrations are correlated with gout and clinical entities such as cardiovascular disease and diabetes. In the genome-wide association study KORA (Kooperative Gesundheitsforschung in der Region Augsburg) F3 500K (n = 1,644), the most significant SNPs associated with uric acid concentrations mapped within introns 4 and 6 of SLC2A9, a gene encoding a putative hexose transporter (effects: -0.23 to -0.36 mg/dl per copy of the minor allele). We replicated these findings in three independent samples from Germany (KORA S4 and SHIP (Study of Health in Pomerania)) and Austria (SAPHIR; Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk), with P values ranging from 1.2 x 10(-8) to 1.0 x 10(-32). Analysis of whole blood RNA expression profiles from a KORA F3 500K subgroup (n = 117) showed a significant association between the SLC2A9 isoform 2 and urate concentrations. The SLC2A9 genotypes also showed significant association with self-reported gout. The proportion of the variance of serum uric acid concentrations explained by genotypes was about 1.2% in men and 6% in women, and the percentage accounted for by expression levels was 3.5% in men and 15% in women.