Northern Chinese Han Population Pon Gene Cluster Potential Functions Of Polymorphic Loci And Coronary Heart Disease Association Studies,

Background: The oxidative modification of low-density lipoprotein in theartery wall is currently believed to be central to the pathogenesis of atherosclerosis. Paraoxonase (PONl), an enzyme located on HDL, can prevent LDL from oxidation at a certain extent. Recent studies show two other members of paraoxonase gene family, P0N2 and PON3, possess antioxidant properties similar to PON1. Several studies have shown that some polymorphisms of PONl and PON2 gene correlated with CHD, whereas others have not. This variability in results might be due to linkage relationships with other unidentified functional genetic variants in this genes cluster, so the aim of the present study was to scan the whole PON gene cluster to identify all putative functional polymorphisms and further to investigate whether these polymorphisms are associated with CHD in Chinese Han population.Methods: Case - control design was applied in this study. Four hundred andfour patients with CHD (case group) were recruited from Fu Wai Cardiovascular Institute between October 1997 and September 1999. 404 individuals (control group) in sex and age group-matched with case group, were randomly selected from subjects participating in a community-based survey of cardiovascular risk factors in Beijing. A set of questionnaires was implemented to obtain detail information covering demographic data, medical history, family history of CHD, drug therapy, cigarette smoking, and alcohol consumption. Weight, height, waistline and hip circumference were recorded, and the body mass index and waist-to-hip ratio were calculated. Two hundred cases and two hundred controls were randomly selected from corresponding group subjects for PONl activity measurement. Common polymorphisms of PON1, PON2 and PON3 gene were identified by directly sequencing of genomic DNAs derived from 48 randomly selected patients. Thirteen polymorphisms were then genotyped in all 808 subjects by sequencing, PCR amplification of specific alleles, or PCR- RFLP.Estimated Haplotype and haplotype pair methods along with genotypes were...