THE CODON-55 POLYMORPHISM IN THE PARAOXONASE-1 GENE IS NOT ASSOCIATEDWITH THE RISK OF CORONARY HEART-DISEASE IN ASIAN INDIANS AND CHINESE

Recently several but not all studies have implicated the codon 192 pol ymorphism in the paraoxonase 1 (PON1) gene with the risk of coronary h eart disease (CHD). These findings suggest that this polymorphism is n ot functional but rather may be in linkage disequilibrium with a funct ional mutation in the PON1 or a nearby gene. In this investigation, we have evaluated the role of another common polymorphism in the PON1 ge ne at codon 55 with the risk of CHD in a biracial sample of Asian Indi ans and Chinese. We observed a significant inter-racial variability in the allelic distribution as the frequency of the less common allele, codon 55/L, was significantly higher in Indians than Chinese (0.202 ve rsus 0.036; P < 0.0001). However, despite this inter-racial difference the codon 55 polymorphism was neither associated with CHD risk nor wi th plasma lipoprotein-lipids variation in both racial groups. We also used two site haplotype data (codons 55 and 192) to assess the combine d contribution of the two polymorphisms to the risk of CHD. There was a strong linkage disequilibrium between the two polymorphic sites in b oth racial groups (P < 0.0001). While the haplotype data revealed no a ssociation with CHD in Chinese, the frequency of the BL haplotype was significantly higher (0.430 versus 0.311; P = 0.004) and the frequency of the AL haplotype was significantly lower (0.368 versus 0.483; P = 0.006) in Indian patients than controls. Since the B allele of the cod on 192 polymorphism was shown to be an independent risk factor for CHD in Indians in our previous study, the positive association of the BL haplotype with CHD appears to be mediated by the B allele with no inde pendent contribution from the codon 55 polymorphism. (C) 1998 Elsevier Science Ireland Ltd.