致动脉粥样硬化性尿酸浓度的遗传相关性存在性别和年龄的交互作用。
Sex and age interaction with genetic association of atherogenic uric acid concentrations.
机构信息
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Schöpfstr. 41, A-6020 Innsbruck, Austria.
出版信息
Atherosclerosis. 2010 Jun;210(2):474-8. doi: 10.1016/j.atherosclerosis.2009.12.013. Epub 2009 Dec 16.
BACKGROUND
High serum uric acid levels are associated with gout, atherosclerosis and cardiovascular disease. Three genes (SLC2A9, ABCG2, and SLC17A3) were reported to be involved in the regulation of uric acid levels.
DESIGN AND METHODS
SNPs rs2231142 (ABCG2) and rs1165205 (SLC17A3) were genotyped in three cohorts (n=4492) and combined with previously genotyped SNPs within SLC2A9 (rs6855911, rs7442295, rs6449213, rs12510549).
RESULTS
Each copy of the minor allele decreased uric acid levels by 0.30-0.38 mg/dL for SLC2A9 (p values: 10(-20)-10(-36)) and increased levels by 0.34 mg/dL for ABCG2 (p=1.1x10(-16)). SLC17A3 influenced uric acid levels only modestly. Together the SNPs showed graded associations with uric acid levels of 0.111 mg/dL per risk allele (p=3.8x10(-42)). In addition, we observed a sex-specific interaction of age with the association of SLC2A9 SNPs with uric acid levels, where increasing age strengthened the association of SNPs in women and decreased the association in men.
CONCLUSIONS
Genetic variants within SLC2A9,ABCG2 and SLC17A3 show highly significant associations with uric acid levels, and for SNPs within SLC2A9 this association is strongly modified by age and sex.
背景
血清尿酸水平升高与痛风、动脉粥样硬化和心血管疾病有关。有三个基因（SLC2A9、ABCG2 和 SLC17A3）被报道参与尿酸水平的调节。
设计和方法
在三个队列（n=4492）中对 SNPs rs2231142（ABCG2）和 rs1165205（SLC17A3）进行基因分型，并与之前在 SLC2A9 内基因分型的 SNPs（rs6855911、rs7442295、rs6449213、rs12510549）相结合。
结果
SLC2A9 的每个 minor 等位基因降低尿酸水平 0.30-0.38mg/dL（p 值：10(-20)-10(-36)），ABCG2 增加 0.34mg/dL（p=1.1x10(-16)）。SLC17A3 对尿酸水平的影响较小。这些 SNP 与尿酸水平呈梯度相关，每个风险等位基因相关 0.111mg/dL（p=3.8x10(-42)）。此外，我们观察到 SLC2A9 SNPs 与尿酸水平的关联存在性别特异性的年龄交互作用，即随着年龄的增加，SNP 与女性尿酸水平的关联增强，与男性的关联减弱。
结论
SLC2A9、ABCG2 和 SLC17A3 内的遗传变异与尿酸水平高度相关，而 SLC2A9 内的 SNP 关联受年龄和性别强烈影响。
Zotero 插件