Genotype Associations with Dyslipoproteinemia in Male Venous Thrombosis Patients

Abstract number: P1189

Pecheniuk¹ NM, Deguchi¹ H, Averell² PM, Elias^1,2 DJ, Griffin JH

^{1,2 11}The Scripps Research Institute, La Jolla, CA, USA ¹¹The Scripps Research Institute, La Jolla, CA, USA ²²Scripps Clinic, La Jolla, CA, USA

Using NMR to quantitate each plasma lipoprotein subclass and ELISAs to measure apolipoproteins, we showed that dyslipoproteinemia is a risk factor for venous thromboembolism (VTE) in males and is characterised by lowered large HDL particles and elevated small LDL particles in plasma. To identify genetic influences contributing to dyslipoproteinemia in VTE patients, we analysed common polymorphisms (SNPs) in the following lipoprotein modulating genes known to alter lipoprotein subclass distribution: hepatic lipase (LIPC -514C/T), endothelial lipase (LIPG T111I), cholesterol ester transfer protein (CETP) (TaqI B and I405V), ApoCIII SstI (nt3238 C/G; 3' UTR) and scavenger receptor class B, type I (SRB1; exon 1 Ser2Gly; exon 8 C/T nt1050). Comparison between male VTE patients (n= 50) and age matched controls did not show any difference in allele frequencies for the LIPC (24.0% vs 21.4%; P= 0.67), LIPG (28.0% vs 32.7%; P= 0.48), CETP I405V (22.0% vs 30.6%; P= 0.17), ApoCIII SstI (0.06% vs 0.09%; P= 0.40) or SRB1 exon 1 (11.0% vs 16.3%; P= 0.28) or SRB1 exon 8 (43.0% vs 43.9%; P= 0.90). However, the CETP TaqI B (B2 allele) was significantly less prevalent for VTE patients compared to controls (32.0% vs 46.9%; P= 0.03). CETP plays an important physiologic role in the transfer of cholesteryl ester from HDL to apoB containing lipoproteins and the TaqI B2 polymorphism has been linked to decreased CETP antigen and activity, resulting in larger HDL and LDL particle sizes and concentration. Thus, the lower CETP TaqI (B2 allele) frequency in VTE is predicted to cause the lower HDL and elevated LDL in male VTE patients. Therefore, CETP TaqI B may pose as a novel genetic risk factor in males causing dyslipoproteinemia in association with venous thrombosis.