DNA polymorphisms in two paraoxonase genes (PON1 and PON2) are associated with the risk of coronary heart disease

American Journal of Human Genetics
D K SangheraM Ilyas Kamboh

Abstract

A common polymorphism at codon 192 in the human paraoxonase (PON) 1 gene has been shown to be associated with increased risk for coronary heart disease (CHD) in Caucasian populations. However, these findings have not been reported consistently in all Caucasian and non-Caucasian populations, suggesting that this is not a functional mutation but may mark a functional mutation present in either PON1 or a nearby gene. Recently, two other PON-like genes, designated "PON2" and "PON3," have been identified, and they are linked with the known PON1 gene on chromosome 7. Identification of additional polymorphisms in the PON-gene cluster may help to locate the functional polymorphism. In this report, we describe the existence of a common polymorphism at codon 311 (Cys-->Ser; PON2*S) in the PON2 gene, as well as its association with CHD alone and in combination with the PON1 codon 192 polymorphism in Asian Indians. The frequency of the PON2*S allele was significantly higher in cases than in controls (.71 vs. .61; P=.016). The age- and sex-adjusted odds ratio (OR) was 2.5 (95% confidence interval &sqbl0;95% CI&sqbr0;=1.8-3.1; P=.0090) for the PON2*S allele carriers. Further stratification of the PON2*S association, on the basis of the prese...Continue Reading

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