PARAOXONASE POLYMORPHISM (GLN(192)-ARG) IS ASSOCIATED WITH CORONARY HEART-DISEASE IN JAPANESE NONINSULIN-DEPENDENT DIABETES-MELLITUS

Serum paraoxonase/arylesterase (PONA) is associated with high-density Lipoprotein and may prevent oxidation of low-density lipoprotein by hy drolyzing lipid peroxides. A recent report suggested an association of glutamine (A type)/arginine (B type) polymorphism at position 192 of PONA gene with coronary heart disease (CHD) among Caucasian patients w ith noninsulin-dependent diabetes mellitus (NIDDM). However, conflicti ng results have also been reported. To investigate the significance of this polymorphism in the pathogenesis of CHD, we performed an associa tion study of this polymorphism with CHD in Japanese NIDDM patients. W e genotyped 164 patients with NIDDM, 42 with CHD, and 122 without CHD. Other known risk factors for CHD were matched between the 2 groups. A B + BB isoforms were detected in 41 of 42 diabetic patients with CHD. The proportion of B allele carriers (AB + BB) was significantly higher than that of AA carriers among diabetic patients with CHD compared wi th those without CHD (chi(2) = 7.68, P = 0.003). Multivariate logistic regression analyses showed a markedly increased odds ratio (OR: 8.823 , CI, 1.13-68.7) in B allele carriers, while ORs of other risk factors remained between 1.01 and 1.92. Carriers of the B allele of the Gln19 2Arg polymorphism in the PONA gene proved to be at increased risk for developing CHD in Japanese NIDDM patients. This association was indepe ndent of other known risk factors for CHD, suggesting an important rol e of the paraoxonase B isoform in the pathogenesis of CHD.