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

ABSTRACT

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. 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. 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. 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