Kanca Deniz, Gormus Uzay, Tokat Bengu, Eronat Allison P, Bugra Zehra, Ozturk Oğuz, Yilmaz-Aydogan Hulya
Department of Molecular Medicine, Institute for Experimental Medicine, Istanbul University, Vakif Gureba c., Capa, 34093, Istanbul, Turkey.
Department of Biochemistry, Istanbul Bilim University, Istanbul, Turkey.
Biochem Genet. 2017 Apr;55(2):168-182. doi: 10.1007/s10528-016-9782-5. Epub 2016 Nov 30.
Recently, subfraction analysis of serum low density lipoprotein (LDL) is considered to be a better predictor of the risk of coronary heart disease (CHD) compared to the other lipid parameters. The aim of this study was to examine the effects of the HDL-associated Taq1B (rs708272) SNP of cholesterol ester transfer protein (CETP) gene on serum LDL subfractions in patients with CHD. Serum lipid levels were measured enzymatically and LDL subfraction analysis was carried out by the Lipoprint System (Quantimetrix, CA, USA). The CETP rs708272 SNP was studied in 66 healthy controls and 79 patients with CHD receiving statin therapy by the PCR-RFLP technique. The CHD patients had elevated antiatherogenic LDL-1 subfraction (p = 0.042), decreased atherogenic IDL-C subfraction (p = 0.023), and total IDL (p = 0.030) levels compared to the healthy controls. The CETP rs708272 Taq1B minor B2 allele was associated with increased levels of antiatherogenic LDL-1 (B2: 0.40 ± 0.20 vs. B1B1: 0.25 ± 0.08, p = 0.004) and large-LDL (LDL 1-2) subfractions in the CHD group (B2 allele: 0.68 ± 0.41 vs. B1B1: 0.42 ± 0.20; p < 0.05), while it was associated with reduced levels of the large-LDL subfraction in healthy subjects (B2 allele: 0.29 ± 0.14 vs. B1B1: 0.54 ± 0.24; p = 0.017). However, there was no statistically significant association between the CETP rs708272 SNP and small dense LDL subfraction (LDL 3-7) and lipoprotein levels (p > 0.05). Our findings have indicated that the CETP rs708272 SNP together with statin therapy may show a favorable effect on antiatherogenic LDL-1 and large-LDL subfractions in CHD patients with an atherogenic effect on large-LDL subfraction in healthy subjects. Based on these results, it can be concluded that the effects of the CETP variation on LDL subfraction could change in cardiometabolic events such as CHD and statin therapy.
最近，与其他血脂参数相比，血清低密度脂蛋白（LDL）亚组分分析被认为是冠心病（CHD）风险的更好预测指标。本研究的目的是检测胆固醇酯转运蛋白（CETP）基因的高密度脂蛋白相关Taq1B（rs708272）单核苷酸多态性（SNP）对冠心病患者血清LDL亚组分的影响。采用酶法测定血脂水平，并通过Lipoprint系统（美国加利福尼亚州Quantimetrix公司）进行LDL亚组分分析。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术对66例健康对照者和79例接受他汀类药物治疗的冠心病患者进行CETP rs708272 SNP研究。与健康对照者相比，冠心病患者具有抗动脉粥样硬化作用的LDL-1亚组分升高（p = 0.042），具有动脉粥样硬化作用的中间密度脂蛋白胆固醇（IDL-C）亚组分降低（p = 0.023），总IDL水平降低（p = 0.030）。CETP rs708272 Taq1B次要B2等位基因与冠心病组中抗动脉粥样硬化的LDL-1水平升高有关（B2：0.40±0.20 vs. B1B1：0.25±0.08，p = 0.004），以及大LDL（LDL 1-2）亚组分升高有关（B2等位基因：0.68±0.41 vs. B1B1：0.42±0.20；p < 0.05），而在健康受试者中，它与大LDL亚组分水平降低有关（B2等位基因：0.29±0.14 vs. B1B1：0.54±0.24；p = 0.017）。然而，CETP rs708272 SNP与小而密LDL亚组分（LDL 3-7）和脂蛋白水平之间无统计学显著关联（p > 0.05）。我们的研究结果表明，CETP rs708-72 SNP与他汀类药物治疗一起可能对冠心病患者的抗动脉粥样硬化LDL-1和大LDL亚组分产生有利影响，而对健康受试者的大LDL亚组分具有动脉粥样硬化作用。基于这些结果，可以得出结论，CETP变异对LDL亚组分的影响在冠心病和他汀类药物治疗等心脏代谢事件中可能会发生变化。
