Investigation on two polymorphisms effective on HDL-C concentration in patients with coronary artery disease using restriction fragment length polymorphism

Background and aim: High density lipoprotein cholesterol (HDL-C) is a known inverse predictor of coronary heart disease (CHD). Cholesteryl ester transfer protein (CETP) and hepatic lipase (HL) are key proteins in HDL-C metabolism so that decreased CETP or HL activity is associated with high HDL-C. -629C/A polymorphism in promoter of CETP gene and-514C/T in promoter of HL gene were previously reported to reduce related protein level in plasma. In this study association of these polymorphisms with CHD related to HDL-C level were investigated. Methods: In this analytical-descriptive study 321 subjects underwent coronary angiography and divided in two groups base on angiogram (non CAD = 135 and CAD = 186). Serum lipids profile was measured by standard procedure and genotype was detected using PCR-RFLP method. Results: Overall the CETP genotype frequencies were in CAD patients: 58.8% (n=110), 28.9% (n=54) and 12.3% (n=23) and in non CAD patients: 45.2% (n=61), 41.5% (n=56) and 13.3% (n=18) for AA, CA and CC respectively. HL genotype frequencies were in CAD patients: 61.6% (n=114), 33.5% (n=62) and 4.9% (n=9) and in non CAD patients: 65.9% (n=89), 27.4% (n=37) and 6.7% (n=9) for CC, CT and TT respectively. In control group HDL-C concentration was higher for AA than CC genotype in -629C/A, and also for TT than CC genotype in -514C/T. Allele A in all subjects and T allele in woman were higher in CAD than non CAD group. A high increase in HDL-C level (10. mg/dl) was observed in individuals with CETP-AA/LIPC-TT and CETP-CA/LIPC-TT relative to CETP-CC/LIPC-CC across all subjects (P< 0.001) but there was no difference in CAD prevalence. Conclusion: Allele A from -629C/A, and T from -514C/T even with the increasing of HDL-C concentration had higher frequency in CAD than non CAD group. Therefore, it seems that HDL-C didn’t protect coronary artery when CETP or HL activity was reduced by these polymorphisms.