GLN-ARG192 POLYMORPHISM OF PARAOXONASE AND CORONARY HEART-DISEASE IN TYPE-2 DIABETES

Paraoxonase is a high-density-lipoprotein-associated enzyme capable of hydrolysing lipid peroxides. Thus it might protect lipoproteins from oxidation. It has two isoforms, which arise from a glutamine (A isofor m) to arginine (B isoform) interchange at position 199. The relevance of this polymorphism to coronary heart disease (CHD) in non-insulin-de pendent diabetic patients was investigated in case-control study. Of t he 434 patients, 171 had confirmed coronary artery disease; the other 263 had no history of such disease. The B allele and AB+BB genotypes w ere associated with an increased risk of coronary heart disease. Compa red with subjects homozygous for the A allele (AA genotype), the odds ratio of CHD for subjects homozygous for the B allele was 2.5 (95% CI 1.2-5.3) and that for those heterozygous for the B allele was 1.6 (95% CI 1.1-2.4), suggesting a codominant effect on cardiovascular risk. W hen subjected to multivariate analysis, the B allele remained signific antly associated with CHD (odds ratio 1.94, p=0.03). The paraoxonase g ene polymorphism is thus an independent cardiovascular risk factor in non-insulin-dependent diabetic patients. A possible explanation for th is finding is that activity of the paraoxonase B isotype does not prot ect well against lipid oxidation, a major atherogenic pathway.