Allelic variants of the human scavenger receptor class B type 1 and paraoxonase 1 on coronary heart disease: Genotype-phenotype correlations

Abstract

Objective— The antioxidant properties of high-density lipoprotein (HDL) have been attributed to paraoxonase (PON) enzyme activity. Human scavenger receptor class B type 1 (SR-BI; CD36 and lysosomal integral membrane protein-II analogous-1 [CLA-1]) plays a central role in HDL-mediated native and oxidized cholesteryl ester uptake. We tested for a significant contribution of common variant of these genes to coronary heart disease (CHD) risk and hypothesized that genetic-mediated PON activity and CLA-1/SR-BI receptor functional properties jointly reduce plasma oxidation status.

Methods and Results— We studied 304 cases and 315 controls. Polymorphisms were analyzed by polymerase chain reaction-restriction fragment analysis. CLA-1/SR-BI-relative expression levels and mRNA stability were analyzed by the comparative threshold cycle method. There was a significant difference in the male genotype distribution of the CLA-1/SR-BI exon 8 (C8/T8) variant between groups with an odds ratio of 1.7 (95% CI, 1.16 to 2.51). This significant risk was restricted to those subject carriers of Arg (R) and Leu (L) allele of the PON1 192 and 55 variants and was confirmed in multiple logistic regression analysis. CLA-1/SR-BI mRNA expression levels differed according to CLA-1/SR-BI genotypes.

Conclusions— These data suggest a plausible genetic interaction between the CLA-1 exon 8 gene polymorphism and the risk of CHD in males.

HDL antioxidant properties have been attributed to the genetic-determined paraoxonase activity. Human scavenger receptor class B type 1 plays a central role in HDL-mediated cholesteryl ester hydroperoxides uptake. We tested for a significant contribution of these genes to coronary disease and analyzed the paraoxonase activity and CLA-1/SR-BI receptor functional properties.