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| Effect of ApoE and SLCO1B1 gene polymorphisms on lipid-lowering therapy in patients with hyperlipidemia |
| LIU Jia1 YOU Jia2 ZHU Hua1 ZHANG Qingyang3 ZHU Ye4▲ |
1.Department of Pharmacy, Northern Jiangsu People’s Hospital, Jiangsu Province, Yangzhou 225001, China;
2.Department of Internal Medicine, Yangzhou Maternal and Child Health Hospital, Jiangsu Province, Yangzhou 225001, China;
3.the First Clinical College, Dalian Medical University, Liaoning Province, Dalian 116044, China;
4.Department of Cardi- ovascular Medicine, Northern Jiangsu People’s Hospital, Jiangsu Province, Yangzhou 225001, China |
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Abstract Objective To explore the polymorphisms of ApoE and SLCO1B1 genes and their effects on the lipid-lowering effect of statins in patients with hyperlipidemia. Methods A total of 247 patients with hyperlipidemia found during routine physical examination in Northern Jiangsu People’s Hospital, Jiangsu Province, from January 2020 to January 2022 were selected, and the polymorphisms of ApoE and SLCO1B1 gene loci of the patients were detected by PCR-pyrosequencing method, and the Hardy-Weinberg law was analyzed for genotype typing. The distribution characteristics of different genotypes in sex were compared. The patients were classified according to ApoE and SLCO1B1 gene polymorphisms, and the differences in blood lipid indexes of patients with different genotypes were compared before and after taking Statins for three months. Results The observed ApoE and SLCO1B1 gene loci in 247 patients with hyperlipidemia were consistent with Hardy-Weinberg law (P＞0.05). The ApoE alleles of the patients were E2 (133 cases), E3 (173 cases), and E4 (41 cases), involving six different genotypes, namely E2/E2, E2/E3, E2/E4, E3/E3, E3/E4, and E4/E4, and there was no statistical significance in the gender distribution of different genotypes (P＞0.05). SLCO1B1 gene phenotypes were detected in three classes (six genotypes), including Class Ⅰ (*1a/*1a, *1a/*1b, *1b/*1b, 185 cases), Ⅱ (*1a/*15, *1b/*15, 58 cases), and Ⅲ (*15/*15, 4 cases) genotypes. The gender distribution of SLCO1B1 genotype patients was compared, and the difference was statistically significant (P＜0.05). After three months of treatment, total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) in ApoE2, E3, and E4 patients were lower than those before treatment, the differences were statistically significant (P＜0.05). After three months of treatment, TC, TG, and LDL-C in SLCO1B1 genotype ClassⅠ, Ⅱ, and Ⅲ patients were lower than those before treatment, and the differences were statistically significant (P＜0.05). Conclusion The gene frequencies of ApoE and SLCO1B1 are regularly distributed, and there are sex differences in the SLCO1B1 genotype. The polymorphism of ApoE and SLCO1B1 genes may have no effect on statin therapy in patients with hyperlipidemia.
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[1] Bu J，Wu Y，Cai X，et al. Hyperlipidemia induces meibomian gland dysfunction [J]. Ocul Surf，2019，17（4）：777-786.
[2] Begcevic Brkovic I，Z?觟hrer B，Scholz M，et al. Simultaneous Mass Spectrometry-Based Apolipoprotein Profiling and Apo- lipoprotein E Phenotyping in Patients with ASCVD and Mild Cognitive Impairment [J]. Nutrients，2022，14（12）：2474.
[3] El Shamieh S，Costanian C，Kassir R，et al. APOE genotypes in Lebanon：distribution and association with hypercholesterolemia and Alzheimer’s disease [J]. Per Med，2019，16（1）： 15-23.
[4] Xiang Q，Chen SQ，Ma LY，et al. Association between SLCO- 1B1T521C polymorphism and risk of statin-induced myopathy：a metaanalysis [J]. Pharmacogenomics J，2018，18（6）：721-729.
[5] Wu H，Huang Q，Yu Z，et al.The SNPs rs429358 and rs7412 of APOE gene are association with cerebral infarction but not SNPs rs2306283 and rs4149056 of SLCO1B1 gene in southern Chinese Hakka population [J]. Lipids Health Dis，2020， 19（1）：202.
[6] Chyu KY，Zhao X，Zhou J，et al. Immunization using ApoB- 100 peptide-linked nanoparticles reduces atherosclerosis [J]. JCI Insight，2022，7（11）：e149741.
[7] Niu RB，Dong XX，Guo LP，et al. Study on the relationship between SLCO1B1 and ApoE gene polymorphisms and the risk of coronary heart disease in the Mongolian population [J]. Clin Exp Hypertens，2021，43（8）：788-792.
[8] 中国成人血脂异常防治指南修订联合委员会.中国成人血脂异常防治指南（2016 年修订版）[J].中华健康管理学杂志，2017，11（1）：7-28.
[9] 蒋昊，杨阳.SLCO1B1基因多态性对辛伐他汀敏感性及个体化剂量预测[J].中华老年心脑血管病杂志，2021，23（9）：950-953.
[10] 尤佳，张清洋，刘佳，等.苏中苏南地区高脂血症人群ApoE基因多态性分析[J].中华老年多器官疾病杂志，2023，22（6）：411- 414.
[11] Serrano-Pozo A，Das S，Hyman BT. APOE and Alzheimer’s disease：advances in genetics，pathophysiology，and therapeutic approaches [J]. Lancet Neurol，2021，20（1）：68-80.
[12] Lanfranco MF，Ng CA，Rebeck GW. ApoE Lipidation as a Therapeutic Target in Alzheimer’s Disease [J]. Int J Mol Sci，2020，21（17）：6336.
[13] Wisniewski T，Drummond E. APOE-amyloid interaction：Therapeutic targets [J]. Neurobiol Dis，2020，138：104784.
[14] Ramsey LB，Gong L，Lee SB，et al. PharmVar GeneFocus：SLCO1B1 [J]. Clin Pharmacol Ther，2023，113（4）：782-793.
[15] Brunette CA，Vassy JL. The role of SLCO1B1 genotyping in lowering cardiovascular risk [J]. Pharmacogenomics，2021， 22（11）：649-656.
[16] Xiang Q，Zhang X，Ma L，et al. The association between the SLCO1B1，apolipoproteinE，and CYP2C9 genes and lipid response to fluvastatin：a metaanalysis [J]. Pharmacogenet Genomics，2018，28：261-267.
[17] Bo■ina T，Ganoci L，Kara■i■ E，et al. ABCG2 and SLCO1B1 gene polymorphisms in the Croatian population [J]. Ann Hum Biol，2022，49（7/8）：323-331.
[18] Zubiaur P，Benedicto MD，Villapalos-García G，et al. SLC- O1B1 Phenotype and CYP3A5 Polymorphism Significantly Affect Atorvastatin Bioavailability [J]. J Pers Med，2021，11（3）：204.
[19] Ragia G，Atzemian N，Maslarinou A，et al. SLCO1B1 c.521 T>C gene polymorphism decreases hypoglycemia risk in sulfonylurea-treated type 2 diabetic patients [J]. Drug Metab Pers Ther，2022，37（4）：347-352.
[20] Zhong Z，Wu H，Li B，et al. Analysis of SLCO1B1 and APOE geneticpolymorphisms in a large ethnic Hakka popu- lation in southern China [J]. J Clin Lab Anal，2018，32：e22408.
[21] 高辉，王杨，陈婉婷，等.SLCO1B1和APOE基因多态性与他汀类药物疗效的相关性[J].实用医学杂志，2019， 35（14）：2300-2303.
[22] Zhou T，Li H，Zhong H，et al. Association of apoE gene polymorphisms with lipid metabolism in renal diseases [J]. Afr Health Sci，2020，20（3）：1368-1381.
[23] 何莎，苟东芸，王文远，等.河北地区汉族心脑血管病患者基因ApoE和SLCO1B1多态性分析[J].中国现代神经疾病杂志，2021，21（5）：400-405.
[24] Sidaraite A，Vilkeviciute A，Glebauskiene B，et al. Association of ApoE haplotype with clinical evidence of pituitary adenoma [J]. Gene，2019，706：154-161.
[25] Huebbe P，Rimbach G. Evolution of human apolipoprotein E（APOE）isoforms：Gene structure，protein function and int- eraction with dietary factors [J]. Ageing Res Rev，2017，37：146-161.
[26] 任晓楠，赵霞，王明生，等.冠心病介入治疗人群ApoE基因多态性及其血脂相关性的临床研究[J].中国医药科学，2023，13（9）：178-182.
[27] 吴妍，韩铨，胡柳，等.瑞舒伐他汀对载脂蛋白E基因敲除动脉粥样硬化小鼠的作用研究[J].中国当代医药，2021，28（24）：24-28，277.
[28] 谢东德，周思婕，黄杰，等.SLCO1B1、APOE基因多态性对瑞舒伐他汀治疗血脂异常超高危动脉粥样硬化性心血管疾病患者的影响[J].中国老年学杂志，2023，43（4）：769-773. |
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