A (192)ARG VARIANT OF THE HUMAN PARAOXONASE (HUMPONA) GENE POLYMORPHISM IS ASSOCIATED WITH AN INCREASED RISK FOR CORONARY-ARTERY DISEASE INTHE JAPANESE

Recent reports have suggested that polymorphisms in the human paraoxon ase (HUMPONA) gene may be a genetic risk factor for coronary artery di sease (CAD) in white populations. However, this association has not ye t been confirmed in other ethnic populations. We studied 75 Japanese p atients with CAD, whose coronary lesions were confirmed by angiography , and 115 Japanese control subjects with no history of CAD and a norma l resting electrocardiogram. The assays for genotyping the two polymor phisms in the HUMPONA gene ((192)Arg/Gln and (55)Leu/ Met) were based on changes in restriction enzyme digestion patterns. For codon 192, th e frequencies of the Arg-coding allele (B allele) in both patients and control subjects were much higher than those from published results o f whites (.26 to .31), and the difference between patients (.74) and c ontrol subjects (.59) was statistically significant (P=.002). The pati ent 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 all el in control subjects and patients were much higher (.91 and .93, res pectively) than those published results for whites, but there was no d ifference between Japanese control subjects and Japanese patients. Whe n subjects with the (55)Leu/Leu genotype only were analyzed, (192)Arg/ Arg homozygotes were still significantly more frequent in the patients than in the control subjects (55.4% vs 37.2%, P=.024), and the freque ncy of the (192)Arg allele was also higher in patients than control su bjects (P=.013). Logistic regression analysis including conventional c oronary risk factors revealed that (192)Arg is an independent risk fac tor for CAD. Thus, in the Japanese, the association of CAD with the (1 92)Arg variant of HUMPONA (B-type enzyme) is similar to that reported for whites, although the allele frequencies for (192)Arg and (55)Leu a re much higher in the former than the latter population.