Zama T, Murata M, Matsubara Y, Kawano K, Aoki N, Yoshino H, Watanabe G, Ishikawa K, Ikeda Y
Department of Medicine, School of Medicine, Keio University, Tokyo, Japan.
Arterioscler Thromb Vasc Biol. 1997 Dec;17(12):3565-9. doi: 10.1161/01.atv.17.12.3565.
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 not 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 .31), 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 patients 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 regression 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.
最近的报告表明，人类对氧磷酶（HUMPONA）基因多态性可能是白种人群冠状动脉疾病（CAD）的一个遗传风险因素。然而，这种关联在其他种族人群中尚未得到证实。我们研究了75例经血管造影证实有冠状动脉病变的日本CAD患者，以及115例无CAD病史且静息心电图正常的日本对照者。对HUMPONA基因中的两个多态性（192Arg/Gln和55Leu/Met）进行基因分型的检测是基于限制性酶切图谱的变化。对于密码子192，患者和对照者中编码Arg的等位基因（B等位基因）频率均远高于已发表的白种人结果（0.26至0.31），患者（0.74）和对照者（0.59）之间的差异具有统计学意义（P = 0.002）。患者组中Arg/Arg（B/B）纯合子的比例更高（52.0%对32.2%，P = 0.006）。对于密码子55，对照者和患者中编码Leu的等位基因频率（分别为0.91和0.93）远高于已发表的白种人结果，但日本对照者和日本患者之间没有差异。仅分析具有55Leu/Leu基因型的受试者时，患者中192Arg/Arg纯合子的频率仍显著高于对照者（55.4%对37.2%，P = 0.024），并且患者中192Arg等位基因的频率也高于对照者（P = 0.013）。包括传统冠状动脉危险因素的逻辑回归分析显示，192Arg是CAD的独立危险因素。因此，在日本人中，CAD与HUMPONA的192Arg变异体（B型酶）的关联与白种人报道的相似，尽管前者中192Arg和55Leu的等位基因频率远高于后者。
