Novel common and rare genetic determinants of paraoxonase activity: FTO, SERPINA12, and ITGAL.

ABSTRACT: 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 asso

SUBMITTER: Kim DS 

PROVIDER: S-EPMC3588879 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature