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巴基斯坦高胆固醇血症和高甘油三酯血症患者中HMGCR和Apo E基因的单核苷酸多态性及其对他汀类药物治疗反应的影响。

SNP of HMGCR and Apo E genes and their impact in response to statin therapy in hypercholesterolemic and hypertriglyceridemic patients in Pakistan.

作者信息

Rizwan Muhammad, Aslam Nosheen, Ashfaq Usman Ali, Hayat Muhammad, Hussain Syed Makhdoom

机构信息

Department of Biochemistry, Government College University, Faisalabad, Pakistan.

Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan.

出版信息

Pak J Pharm Sci. 2021 Jul;34(4(Supplementary)):1577-1583.

Abstract

Coronary artery disease (CAD) and the problems associated with it are the most prominent causes of death in the whole world. Statins are accustomed to lower lipid levels in CAD patients. The target of this study was to analyze whether or not common variations in HMGCoA Reductase (HMGCR) and Apolipoprotein E (ApoE) genes are responsible for metabolism of lipid and statin that modify the impact of statins on serum level of lipids and lipoprotein concentrations in Coronary heart disease patients. One hundred CAD patients were registered for the study. At the start of the study biochemical measurements were performed to work out the baseline levels. Patients were treated with twenty mg Lipitor for one month and biochemical measurements were tested again. According to the post-treatment, LDL-c levels, patients were divided into a pair of group as non-responders and responders, independently. The information concerning the risk factors like smoking, alcohol consumption etc. was conjointly obtained. DNA was extracted from peripheral blood. The presence of rs17244841 and rs17238540 mutations in HMGCR and έ2, έ3 and έ4 variants of ApoE were settled by performing RT-PCR. Results were assessed statistically. HMGCR mutations were principally found in responders and ε4 variant of ApoE was principally found in non-responders. It was found that the presence of HMGCR mutations causes a big reduction in total cholesterol and LDL-c levels. Conjointly, the presence of έ2 variant of Apo E causes a statistically vital increase in triglyceride levels. Our findings should be investigated by different researchers to clarify the mechanism.

摘要

冠状动脉疾病(CAD)及其相关问题是全球最主要的死亡原因。他汀类药物常用于降低CAD患者的血脂水平。本研究的目的是分析HMGCoA还原酶(HMGCR)和载脂蛋白E(ApoE)基因的常见变异是否负责脂质和他汀类药物的代谢,从而改变他汀类药物对冠心病患者血脂和脂蛋白浓度的影响。一百名CAD患者登记参加了该研究。在研究开始时进行生化测量以确定基线水平。患者接受20毫克立普妥治疗一个月,然后再次进行生化测量。根据治疗后低密度脂蛋白胆固醇(LDL-c)水平,患者被独立分为无反应者和反应者两组。还收集了有关吸烟、饮酒等危险因素的信息。从外周血中提取DNA。通过进行逆转录聚合酶链反应(RT-PCR)确定HMGCR中rs17244841和rs17238540突变以及ApoE的ε2、ε3和ε4变体的存在情况。对结果进行统计学评估。HMGCR突变主要见于反应者,而ApoE的ε4变体主要见于无反应者。发现HMGCR突变的存在会导致总胆固醇和LDL-c水平大幅降低。此外,ApoE的ε2变体的存在会导致甘油三酯水平在统计学上显著升高。我们的研究结果应由不同的研究人员进行调查以阐明其机制。

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