Additive Antiatherogenic Effects of CETP rs708272 on Serum LDL Subfraction Levels in Patients with CHD Under Statin Therapy

Abstract

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.

MassARRAY Multigene Screening Combined with LDL-C and sdLDL-C Detection for more Favorable Outcomes in type 2 Diabetes Mellitus Therapy

“…Many studies have shown that gene polymorphisms in uence T2DM therapeutic effects [16][17][18][19][20][21][22][23]. SNPs in the HTR3B, HTR7 or ABCB1 genes were associated with myalgia or liver injury [16,22].…”

“…APOE and HMGCR mutations were associated with LDL-C levels [17,20]. CETP, KIF6, SLCO1B1, and CYP2C9*3 were related to the statin effect [18,19,21,23]. To check genetic polymorphisms in Chinese T2DM patients, HTR3B (rs2276307, A > G), APOE (rs7412, c.526C > T), APOE (rs429358, c.388T > C), CYP2C9*3 (rs1057910, c.1075A > C), KIF6 (rs20455, c.2155T > C), HMGCR (rs17238540, T > G), HMGCR (rs17244841, A > T), ABCB1 (rs2032582, c.2677G > T/A), HTR7 (rs1935349, C > T), SLCO1B1 (rs4149056, c.521T > C), and CETP (rs708272, G > A) were detected by the MassARRAY system before patients underwent statin therapy ( Fig.…”

Small, dense LDL

“…It has been reported that the effects of the cholesterol ester transfer protein (CETP) variation on LDL subfraction could change in conditions such as coronary heart disease (CHD) and statin therapy. This was based on the findings [27] that the CETP rs708272 single nucleotide polymorphisms together with statin therapy may show a favourable effect on antiatherogenic LDL-1 and large-LDL subfractions in CHD patients with an atherogenic effect on large LDL subfraction in healthy patients.…”

MassARRAY multigene screening combined with LDL-C and sdLDL-C detection for more favorable outcomes in type 2 diabetes mellitus therapy

“…Statins are a common prescription medication for cholesterol reduction, and several intervention trials with statins have demonstrated the bene cial effect of lowering LDL-C in both primary and secondary CVD prevention, especially in subjects with T2DM [15,16]. To ensure the T2DM treatment effect, genetic testing was recommended to patients before medication administration [17][18][19][20][21][22][23][24]. SNPs in the HTR3B and HTR7 genes were signi cantly associated with the myalgia score and may affect the development of myalgia in statin-treated patients [17].…”

“…ABCB1 (rs2032582: 2677G > T/A) was signi cantly associated with atorvastatin-induced liver injury (p = 0.00068) [23]. CETP rs708272 SNP together with statin therapy may show a favorable antiatherogenic effect [24].…”