冠心病患者胆固醇逆转运调节基因三磷酸腺苷结合转运子A1的表达研究

Difference of ATP-binding cassette transporter A1 gene expression in patients with and without coronary artery disease

目的观察冠心病患者及非冠心病患者外周血单核细胞三磷酸腺苷结合盒转运子A1(ABCA1)的信使RNA表达差异;观察冠心病患者及非冠心病患者诱导ABCA1基因转录的肝X受体(LXR)的mRNA表达差异。方法接受过冠状动脉造影检查的患者(共58例),根据造影结果分为冠心病组(36例)和非冠心病组(22例)。所有患者均抽取空腹外周静脉血并分离、提取单核细胞RNA;逆转录PCR法检测血样中ABCA1的mRNA表达及LXR的mRNA表达。结果 (1)冠心病组ABCA1的mRNA表达水平显著低于非冠心病组[(0.35±0.17)μg/μlvs.(0.66±0.26)μg/μl,P<0.05],而LXRmRNA的表达未见统计学差异[(0.76±0.31)μg/μlvs.(0.56±0.34)μg/μl,P=0.80]。(2)ABCA1的mRNA表达随糖基化血红蛋白(HbA1c)的增加而降低(r=-0.55,P<0.05)。结论冠心病患者中外周血白细胞ABCA1的基因表达较非冠心病患者显著下降;冠心病患者ABCA1表达的调控机制可能不完全依赖于LXR的方式。ABCA1的mR-NA表达与HbA1c呈显著负相关,HbA1c可能是影响其表达的重要因素之一。

Objective To compare the difference of the mRNA expression of ABCA1 in patients with and without coronary artery disease(CAD).To observe the expression of liver X receptor(LTR)in patients with and without CAD.Methods Patients who accepted the examination of coronary angiography and computer tomography of coronary artery were recruited in our study,and were divided into CAD group(n=36)or non-CAD group(n=22).2 ml peripheral venous blood were collected from all participants,and RNA was extracted from the mononuclear leukocytes by the RNA kit.Quantitative RT PCR was used to measure the mRNA expression of ABCA1 and LXR.Results(1)The mRNA expression of ABCAl was significantly decreased in CAD group[(0.35±0.17)μg/μl vs.(0.66±0.26)μg/μl,P<0.05]compared with non-CAD group,while no diffence of LXR mRNA expression was found between the two groups[(0.76±0.31)μg/μl vs.(0.56±0.34)μg/μl,P=0.80].(2)The level of HbA1c is negatively related with expression of ABCA1(r=-0.55,P<0.05)after multiple linear regression analysis.Conclusions The expression of ABCAl is significantly down-regulated in CAD subjects.The transactivation of the ABCA1 in CAD patients might have other promoters except liver X receptor.HbA1c negatively correlate with the expression of ABCA1.