LDLR基因多态性与瑞舒伐他汀改善颈动脉粥样硬化的相关性
| 作者: |
1孟令婷,
2孙建梅,
3徐寅
1 内蒙古医科大学附属医院药剂部，呼和浩特 010050 2 内蒙古医科大学附属医院骨科A区，呼和浩特 010050 3 内蒙古第四医院内五科，呼和浩特 010080 |
| 通讯: |
徐寅
Email: 418207555@qq.com |
| DOI: | 10.3978/j.issn.2095-6959.2019.05.007 |
摘要
目的：分析低密度脂蛋白受体(low-density lipoprotein receptor，LDLR)rs688基因多态性分布与瑞舒伐他汀治疗颈动脉粥样硬化(carotid atherosclerosis，CAS)患者临床疗效的关系。方法：选取缺血性脑血管病(ischemic cerebrovascular disease，ICVD)患者360例，依据CAS分为两组：研究组 170例，确诊存在CAS；对照组190例，颈动脉无粥样硬化斑块。两组均接受瑞舒伐他汀药物治疗1年，均取血液样本提取基因组DNA，应用聚合酶链反应-限制性片断长度多态性技术对所有样本LDLR rs688基因进行基因型分布和等位基因频率分析。采用彩色多普勒检测两组患者的颈动脉内膜中层厚度(intima-media thickness，IMT)，检测两组血清TG，TC，LDL-C及HDL-C浓度。应用多元logistic回归分析LDLR rs688基因多态性与CAS患者IMT的相关性。结果：与对照组相比，研究组的IMT，TC，LDL-C显著升高，HDL-C显著降低(P<0.05)，而TG差异无统计学意义(P>0.05)。与对照组相比，研究组TT及CC基因型比例显著降低(P<0.05)，TC基因型比例显著升高(P<0.05)；研究组等位基因C频率显著升高(P<0.05)，T频率显著降低(P<0.05)。多元logistic回归分析显示：TC基因型与T等位基因频率是CAS患者IMT的易感因素(P<0.05)。不同基因型CAS患者的TC，LDL-C及IMT(TC>TT>CC，P<0.05)和HDL-C(TC0.05)。结论：LDLR rs688 基因多态性与ICVD患者应用瑞舒伐他汀治疗的CAS密切相关，并且基因型为TC的CAS患者应用瑞舒伐他汀治疗斑块改善最不明显。
关键词：
颈动脉粥样硬化；低密度脂蛋白受体基因；瑞舒伐他汀；基因多态性
Correlation of the atherosclerotic plaque and LDLR gene rs688 polymorphisms in patients with carotid atherosclerosis received by rosuvastatin
CorrespondingAuthor: XU Yin Email: 418207555@qq.com
DOI: 10.3978/j.issn.2095-6959.2019.05.007
Abstract
Objective: To analyze the correlation of the atherosclerotic plaque and LDLR rs688 gene polymorphisms in patients with carotid atherosclerosis received by rosuvastatin. Methods: A total of 360 patients diagnosed to ischemic cerebrovascular disease (ICVD) were selected and divided into two groups according to diagnosing to carotid atherosclerosis, which were research group (170 cases, diagnosed to carotid atherosclerosis) and a control group (190 cases, excluded carotid atherosclerosis). All patients were receiving the treatment by rosuvastatin and the course was one year. The genes DNA of blood samples in two groups were extracted. The LDLR rs688 genotypes and alleles in two groups were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The indexes of carotid intima-media thickness (IMT) of two groups were determined by color Doppler ultrasound. The serum levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were detected by automatic biochemical analyzer. The relationship of the genetic polymorphisms of LDLR rs688 and the carotid atherosclerosis in patients with CHD received by rosuvastatin was analyzed by the logistic regression. Results: Compared to control group, the serum levels of IMT, TC and LDL-C in research group were higher (P<0.05), and the serum levels of HDL-C in research group were lower (P<0.05), but the serum levels of TG were no different between two groups (P>0.05). Compared to control group, the frequencies of TT and CC genotype in research group were lower (P<0.05), and the frequencies of TC genotype were higher (P>0.05); the allele frequency of C in research group were higher (P<0.05), and the allele frequency of T were lower (P>0.05). The Logistic regression result showed that TC genotype and T allele were the risk factors to the carotid atherosclerosis of the patients with CHD received by rosuvastatin (P<0.05). The levels of TC, LDL-C and IMT at three kinds of genotypes were different, which were TC>TT>CC (P<0.05), and the sequence of HDL-C was TC0.05). Conclusion: The polymorphisms on LDLR rs688 gene is related to the carotid atherosclerosis of the patients with ICVD, and the carotid atherosclerosis degree of patients received by rosuvastatin with TC genotype of LDLR rs688 gene is more serious.
Keywords：
carotid atherosclerosis; low density lipoprotein receptor gene; rosuvastatin; genetic polymorphism