Human Paraoxonase1 Gene Polymorphisms and the Risk of Coronary Heart Disease: A Community-Based Study

Abstract

Published data on the association between paraoxonase1 (PON1) polymorphisms and coronary heart disease (CHD) have yielded controversial results. The objective of this study was to determine the possible relationship between the two human PON1 amino acid variants, the Leu55Met and the Gln192Arg polymorphism, and the risk of CHD in a community-dwelling cohort of European ancestry. PON1 genotypes of 152 women and 151 men out of 1,998 randomly selected individuals aged 44–75 years were determined by polymerase chain reaction-based restriction enzyme digestion. Study participants underwent cardiological examination including a structured clinical interview, resting ECG, exercise testing and echocardiography. The diagnosis of CHD was based on history and/or appropriate findings during cardiac examination. Evidence for CHD was found in 43 (14.2%) study participants. The Leu/Leu (LL), Leu/Met (LM) and Met/Met (MM) genotypes at position 55 were noted in 131 (43.2%), 128 (42.2%) and 44 (14.5%) subjects; the Gln/Gln (QQ), Gln/Arg (QR) and Arg/Arg (RR) genotypes at codon 192 occurred in 167 (55.1%), 118 (38.9%) and 18 (5.9%) individuals, respectively. Homozygosity for the 55L-allele was significantly associated with CHD (p = 0.02), while the Gln192Arg polymorphism had no effect (p = 0.16). Logistic regression analysis demonstrated age (odds ratio 1.06/year), smoking (odds ratio 2.86), HDL cholesterol (odds ratio 0.94/mg/dl) and the paraoxonase LL genotype (odds ratio 2.25) to be significant predictors of CHD. These data suggest that the paraoxonase LL genotype at position 55 may present a risk factor for CHD.

The Human Paraoxonase Gene Cluster As a Target in the Treatment of Atherosclerosis

“…The PON1 activity in patients with CHD is approximately half that in disease-free control participants (28). Low PON1 activity increases the development of atherosclerosis (353). The group of men with the highest levels of serum PON1 activity were nearly 60% less likely to have CHD than those with the lowest (205).…”

“…However, some studies claim that no association between PON1 polymorphisms and plasma lipoproteins exists (48,204,353). Contradictions among the results from different studies could result from partially intrinsic differences in serum PON levels among populations.…”

“…PON1 polymorphisms and CHD. In recent years, a relationship between the PON1 192 polymorphism and CHD has been proposed (142,253), although some studies have reported no association between PON genotype and CHD risk (128,353). Such dichotomies often occur with association studies, which are thought to have several biases (196).…”

Distribution of Pon L/M55 and Q/R192 Genotypes in Turkish Patients with Angiographically-Defined Coronary Artery Disease: Effects on Serum Lipids

“…35,36 However, other studies showed no association between these PON polymorphisms and plasma lipoproteins. 37,38 A study investigating the association between PON192 polymorphism and serum lipid levels in Turkish CAD patients also failed to show any significant results. 29 In the present study, regarding the comparison of serum lipid levels between CAD patients and the controls with regard to polymorphic allele, the most significant results were in HDL levels.…”

Paraoxonase 1 R/Q alleles are associated with differential accumulation of saturated versus 20:5n3 fatty acid in human adipose tissue

“…Genetic epidemiology studies on the polymorphisms L55M and Q192R have previously reported confl icting data regarding effects on plasma lipoproteins (30)(31)(32). A specifi c search in the published genome wide association studies found no reported association of the PON1 genetic locus with lipids, BP, or any other of the reported parameters.…”