Department of Clinical Biochemistry, Fertility and Infertility Research Center, Kermanshah University of Medical Sciences, Daneshgah Avenue, P.O. Box 67148, Kermanshah, 69914, Iran.
Mol Biol Rep. 2010 Apr;37(4):2083-91. doi: 10.1007/s11033-009-9666-4. Epub 2009 Aug 15.
We have previously shown that butyrylcholinesterase-K (BCHE-K, G1615A/Ala539Thr) variant increases the risk of coronary artery disease (CAD). In addition, we have found that the presence of APOE-epsilon 4 allele augments the risk of CAD in patients with type II diabetes mellitus (T2DM/CAD). Here we explored the concomitant presences of two alleles of the BCHE-K and APOE-epsilon 4 in increasing the risk of CAD or diabetes in T2DM patients with or without CAD and CAD patients without T2DM. This case-control study comprised 631 subjects undergoing their first coronary angiography. They were matched and randomly assigned into four groups: type II diabetic patients with no sign of CAD (T2DM), type II diabetic patients with CAD/ND (T2DM/CAD), CAD patients with no sign of diabetes (CAD/ND), and healthy individuals (NCAD/ND). BCHE-K variant and APOE genotypes were detected by PCR-RFLP and serum lipid level was measured enzymatically. We found that BCHE-K and APOE-epsilon 4 allele act synergistically to increase the risk of CAD in both T2DM, non-diabetic and total CAD (TCAD = T2DM/CAD + CAD/ND) individuals. The level of synergy 1.5 and 1.2 fold are higher in CAD patients (OR = 4.5; P = 0.011) with T2DM than the non-diabetic CAD patients (OR = 3.07; P = 0.024) and TCAD patients (OR = 3.74; P = 0.018), respectively. The CAD subjects with and without T2DM and TCAD patients carrying both APOE-epsilon 4 allele and BCHE-K had significantly lower plasma HDL-C (P values = 0.008, 0.047, and 0.036, respectively) and higher plasma LDL-C (P values = 0.025, 0.048, and 0.04, respectively), than that of the control carriers both APOE-epsilon 4 and BCHE-K. We have found that BCHE-K and APOE-epsilon 4 allele not only act synergistically to increase the risk of CAD, particularly in T2DM subjects in population from western Iran, who have high levels of LDL-C and low levels of HDL-C, suggesting that a specific therapeutic intervention should be considered for these particular groups of patients.
我们之前已经证明，丁酰胆碱酯酶-K（BCHE-K，G1615A/Ala539Thr）变体增加了冠状动脉疾病（CAD）的风险。此外，我们发现 APOE-epsilon 4 等位基因的存在会增加 2 型糖尿病（T2DM/CAD）患者患 CAD 的风险。在这里，我们探讨了 BCHE-K 和 APOE-epsilon 4 两个等位基因的同时存在是否会增加 T2DM 患者伴或不伴 CAD 以及无 T2DM 的 CAD 患者患 CAD 或糖尿病的风险。这项病例对照研究包括 631 名接受首次冠状动脉造影的患者。他们进行了匹配并随机分为四组：无 CAD 迹象的 2 型糖尿病患者（T2DM）、有 CAD/ND 的 2 型糖尿病患者（T2DM/CAD）、无糖尿病迹象的 CAD 患者（CAD/ND）和健康个体（NCAD/ND）。通过 PCR-RFLP 检测 BCHE-K 变体和 APOE 基因型，并通过酶法测量血清脂质水平。我们发现，BCHE-K 和 APOE-epsilon 4 等位基因协同作用，增加了 T2DM、非糖尿病和总 CAD（TCAD = T2DM/CAD + CAD/ND）个体患 CAD 的风险。CAD 患者（OR = 4.5；P = 0.011）中协同作用的水平为 1.5 倍，高于非糖尿病 CAD 患者（OR = 3.07；P = 0.024）和 TCAD 患者（OR = 3.74；P = 0.018）。携带 APOE-epsilon 4 等位基因和 BCHE-K 的有和无 T2DM 的 CAD 患者以及 TCAD 患者的血浆 HDL-C 显著降低（P 值分别为 0.008、0.047 和 0.036），而血浆 LDL-C 显著升高（P 值分别为 0.025、0.048 和 0.04），与对照组携带者的 APOE-epsilon 4 和 BCHE-K 相比。我们发现，BCHE-K 和 APOE-epsilon 4 等位基因不仅协同作用增加 CAD 的风险，特别是在伊朗西部人群中，这些人群 LDL-C 水平高，HDL-C 水平低，这表明应该考虑针对这些特定患者群体的特定治疗干预措施。
