Year: 2012
Type: article
Study design: Observational Study
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.
Source: Journal of Lipids
DOI: 10.1155/2012/189681
Institution: Texas Biomedical Research Institute
Language: English
Subfield: Clinical Biochemistry
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $950
Awards: G140538419, G2048638135, G2063105260, Quantitative Trait Locus Mapping in Human Pedigrees, G2169778925, G220423607, G2751216088, G2795148621, EXTRAMULAR RESEARCH FACILITIES CONSTRUCTION, G4329124214, G4602720886, G5114052566, G518778165, G5222317382, Genetics of Brain Structure and Function: Genome-Wide Association, G5945470964, G5953798225, G6253890364, MOLECULAR AND BIOCHEMICAL GENETICS LABORATORY RENOVATION, G7392605009, G7894334835, G879628117, G9000110552, G9000116647, G9000121831
OpenAlex ID: W2160786152