Wang Jie, Zhang Yun, Yang Zhi-jian, Zhu Tie-bing, Wang Lian-sheng, Chen Bo, Cao Ke-jiang, Huang Jun, Ma Wen-zhu, Jia En-zhi
Department of Epidemiology and Biostatistics, Nanjing Medical University, Nanjing 210029, China.
Acta Pharmacol Sin. 2008 Jun;29(6):736-44. doi: 10.1111/j.1745-7254.2008.00798.x.
To explore the association between 801C>T and 847C>T polymorphisms of the human carboxypeptidase E (CPE) gene exon5, which could cause hyperproinsulinemia, and the angiographical characteristics of coronary atherosclerosis.
In total, 1044 consecutive patients who underwent coronary angiography for suspected or known coronary atherosclerosis were examined with respect to their genotypes, insulin, proinsulin level, and other risk factors of coronary atherosclerosis. The angiographical characteristics of coronary atherosclerosis (ie the severity of coronary heart disease) were defined by Gensinios score (GS) system.
The results showed that the genotype frequencies of CC, CT, and TT at 801C>T locus were significantly different among the patients of the 4 groups who were classified by quartile values of GS (P=0.033). However, the frequency of the 847T allele was 0 for all the patients. The ordinal logistic regression analysis revealed that the increased risk of angiographical characteristics of coronary atherosclerosis were associated with CPE 801CT/TT variant genotypes [adjusted odds ratio (OR)=1.23, 95% confidence interval (CI) =0.93-1.63 for 801CT and adjusted OR=3.13, 95% CI=1.18-8.28 for 801TT] compared with the 801CC wild-type homozygotes. A stratification analysis showed that the effects of the CPE 801TT genotype were more evident among subgroups with relatively older (> or = 60 years) patients, males, and smokers. Furthermore, an analysis of covariance controlling age, sex, and body mass index indicated that differences of blood glucose, insulin, insulin resistance, and the proinsulin level between 801C>T genotype groups were not statistically significant.
These findings indicate that the 801C>T polymorphism in the CPE exon5 gene may contribute to the angiographical characteristics of coronary atherosclerosis in the Chinese population.
探讨人羧肽酶E（CPE）基因外显子5的801C>T和847C>T多态性（可导致高胰岛素原血症）与冠状动脉粥样硬化血管造影特征之间的关联。
对1044例因疑似或已知冠状动脉粥样硬化而接受冠状动脉造影的连续患者进行了基因型、胰岛素、胰岛素原水平及其他冠状动脉粥样硬化危险因素的检测。冠状动脉粥样硬化的血管造影特征（即冠心病的严重程度）采用Gensini评分（GS）系统进行定义。
结果显示，根据GS四分位数对患者进行分组，4组患者在801C>T位点的CC、CT和TT基因型频率存在显著差异（P=0.033）。然而，所有患者中847T等位基因的频率均为0。有序逻辑回归分析显示，与801CC野生型纯合子相比，CPE 801CT/TT变异基因型与冠状动脉粥样硬化血管造影特征风险增加相关[801CT的调整优势比（OR）=1.23，95%置信区间（CI）=0.93-1.63；801TT的调整OR=3.13，95%CI=1.18-8.28]。分层分析显示，CPE 801TT基因型的影响在年龄较大（≥60岁）患者、男性和吸烟者的亚组中更为明显。此外，控制年龄、性别和体重指数的协方差分析表明，801C>T基因型组之间的血糖、胰岛素、胰岛素抵抗和胰岛素原水平差异无统计学意义。
这些发现表明，CPE外显子5基因中的801C>T多态性可能与中国人群冠状动脉粥样硬化的血管造影特征有关。
