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Paraoxonase Polymorphism (Gln¹⁹²-Arg) Is Associated with Coronary Heart Disease in Japanese Noninsulin-Dependent Diabetes Mellitus

Institute of Clinical Medicine (M.O., Y.T., K.Y.), University of Tsukuba, Ibaraki, Japan; The Wellcome Trust Centre for Human Genetics (M.O.), University of Oxford, Oxford, United Kingdom

Address correspondence and requests for reprints to: Masato Odawara, The Wellcome Trust Centre for Human Genetics, University of Oxford, Windmill Road, Oxford, OX3 7BN, United Kingdom.

Serum paraoxonase/arylesterase (PONA) is associated with high-density lipoprotein and may prevent oxidation of low-density lipoprotein by hydrolyzing 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 with noninsulin-dependent diabetes mellitus (NIDDM). However, conflicting results have also been reported. To investigate the significance of this polymorphism in the pathogenesis of CHD, we performed an association study of this polymorphism with CHD in Japanese NIDDM patients. We genotyped 164 patients with NIDDM, 42 with CHD, and 122 without CHD. Other known risk factors for CHD were matched between the 2 groups. AB+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 with those without CHD (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 Gln192Arg polymorphism in the PONA gene proved to be at increased risk for developing CHD in Japanese NIDDM patients. This association was independent of other known risk factors for CHD, suggesting an important role of the paraoxonase B isoform in the pathogenesis of CHD.

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