A ¹⁹²Arg variant of the human paraoxonase (HUMPONA) gene polymorphism is associated with an increased risk for coronary artery disease in the Japanese

Recent reports have suggested that polymorphisms in the human paraoxonase (HUMPONA) gene may be a genetic risk factor for coronary artery disease (CAD) in white populations. However, this association has nor yet been confirmed in other ethnic populations. We studied 75 Japanese patients with CAD, whose coronary lesions were confirmed by angiography, and 115 Japanese control subjects with no history of CAD and a normal resting electrocardiogram. The assays for genotyping the two polymorphisms in the HUMPONA gene (¹⁹²Arg/Gln and ⁵⁵Leu/Met) were based on changes in restriction enzyme digestion patterns. For codon 192, the frequencies of the Arg-coding allele (B allele) in both patients and control subjects were much higher than those from published results of whites (.26 to 131), and the difference between patients (.74) and control subjects (.59) was statistically significant (P=.002). The patient group had a higher proportion of Arg/Arg (B/B) homozygotes (52.0% vs 32.2%, P=.006). For codon 55, the frequencies of the Leu-coding allele in control subjects and pat ants were much higher (.91 and .93, respectively) than those published results for whites, but there was no difference between Japanese control subjects and Japanese patients. When subjects with the ⁵⁵Leu/Leu genotype only were analyzed, ¹⁹²Arg/Arg homozygotes were still significantly more frequent in the patients than in the control subjects (55.4% vs 37.2%, P=.024), and the frequency of the ¹⁹²Arg allele was also higher in patients than control subjects (P=.013). Logistic regress on analysis including conventional coronary risk factors revealed that ¹⁹²Arg is an independent risk factor for CAD. Thus, in the Japanese, the association of CAD with the ¹⁹²Arg variant of HUMPONA (B-type enzyme) is similar to that reported for whites, although the allele frequencies for ¹⁹²Arg and ⁵⁵Leu are much higher in the former than the latter population.