文章基本信息

标题：Novel common and rare genetic determinants of paraoxonase activity: FTO, SERPINA12, and ITGAL
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作者：Daniel S. Kim ; Amber A. Burt ; David R. Crosslin 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2013
卷号：54
期号：2
页码：552-560
DOI：10.1194/jlr.P033266
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：HDL-associated paraoxonase 1 (PON1) activity is associated with cardiovascular and other human diseases. As the role of genetic variants outside of the PON gene cluster on PON1 activity is unknown, we sought to identify common and rare variants in such loci. We typed 33,057 variants on the CVD chip in 1,362 subjects to test for their effects on adjusted-PON1 activity. Three novel genes ( FTO , ITGAL , and SERPINA12 ) and the PON gene cluster had SNPs associated with PON1 arylesterase (AREase) activity. These loci were carried forward for rare-variant analysis using Exome chip genotypes in an overlapping subset of 1,051 subjects using sequence kernel association testing. PON1 ( P = 2.24 × 10⁻⁴), PON3 ( P = 0.022), FTO ( P = 0.019), and SERPINA12 ( P = 0.039) had both common and rare variants associated with PON1 AREase. ITGAL variants were associated with PON1 activity when using weighted sequence kernel association testing (SKAT) analysis ( P = 2.63 × 10⁻³). When adjusting for the initial common variants, SERPINA12 became marginally significant ( P = 0.09), whereas all other findings remained significant ( P FTO , SERPINA12 , and ITGAL predict PON1 activity. These results further link PON1 to diabetes and inflammation and may inform the role of HDL in human disease.
关键词：exome chip ; atherosclerosis ; diabetes