Table of Contents Author Guidelines Submit a Manuscript
Journal of Lipids
Volume 2012, Article ID 189681, 7 pages
http://dx.doi.org/10.1155/2012/189681
Research Article

Novel Associations of Nonstructural Loci with Paraoxonase Activity

Department of Genetics, Texas Biomedical Research Institute, P.O. Box 760549, San Antonio, TX 78245-0549, USA

Received 22 January 2012; Accepted 19 February 2012

Academic Editor: Mira Rosenblat

Copyright © 2012 Ellen E. Quillen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The high-density-lipoprotein-(HDL-) associated esterase paraoxonase 1 (PON1) is a likely contributor to the antioxidant and antiatherosclerotic capabilities of HDL. Two nonsynonymous mutations in the structural gene, PON1, have been associated with variation in activity levels, but substantial interindividual differences remain unexplained and are greatest for substrates other than the eponymous paraoxon. PON1 activity levels were measured for three substrates—organophosphate paraoxon, arylester phenyl acetate, and lactone dihydrocoumarin—in 767 Mexican American individuals from San Antonio, Texas. Genetic influences on activity levels for each substrate were evaluated by association with approximately one million single nucleotide polymorphism (SNPs) while conditioning on PON1 genotypes. Significant associations were detected at five loci including regions on chromosomes 4 and 17 known to be associated with atherosclerosis and lipoprotein regulation and loci on chromosome 3 that regulate ubiquitous transcription factors. These loci explain 7.8% of variation in PON1 activity with lactone as a substrate, 5.6% with the arylester, and 3.0% with paraoxon. In light of the potential importance of PON1 in preventing cardiovascular disease/events, these novel loci merit further investigation.