Paraoxonase-1 L55M Polymorphism with Fatty Acid Composition of Phospholipids in High-Density Lipoproteins

Background: Paraoxonase-1 (PON1) moves with high-density lipoprotein (HDL) particles in blood and prevents low-density lipoprotein (LDL) particles from oxidation. The aims of this study were to investigate the correlation between fatty acid composition of HDL phospholipids with pon-1 polymorphisms and response to lovastatin treatment in people with high blood cholesterol. Methods: In this descriptive study, 265 patients were selected and divided into two groups based on LDL-C concentrations; 131 patients with LDL-C greater than 130 mg/dl (cases) and 134 patients with LDL-C lower than 130 mg/dl (controls). Fatty acids of HDL phospholipids were measured with gas chromatography and lipid profile (cholesterol, triglyceride, LDL-C, HDL-C), apolipoprotein A1 and apolipoprotein B were measured by relevant commercial kits. Oxidized LDL was measured by ELISA method and activity of paraoxonase was determined by a relevant standard manual method. Genotypes of L55M polymorphism were determined by polymerase chain reaction-restriction fragment length polymorphism procedure. Results: Prevalence of L allele from L55M polymorphism was 0.65 and 0.53 in the case and control groups, respectively (P=0.04). PON1 paraoxonase activity in LL homozygote genotype was higher than other genotypes upon treatment with lovastatin. Concentrations of oleic, linoleic and eicosapentaenoic acids in LL genotype were increased by lovastatin administration. Conclusion: Allele (L) from L55M polymorphism had a higher frequency in patients with higher LDL-C concentrations. PON1 genotypes seemed to have a modifying role on paraoxonase-1 activity after lovastatin therapy

Combined Hepatic Lipase-514C/T and Cholesteryl Ester Transfer Protein I405V Polymorphisms Are Associated with the Risk of Coronary Artery Disease

Hepatic lipase (LIPC) and cholesteryl ester transfer protein (CETP) are important components of high-density lipoprotein (HDL) metabolism and reverse cholesterol transport. Therefore, their genes are promising candidate genes for cardiovascular disease. The aim of the present study was to investigate whether combined LIPC -514C/T and CETP I405V polymorphisms correlate with angiographically documented coronary artery disease (CAD). Genotyping was performed in 317 patients who underwent clinically indicated coronary angiography. The patients were classified with significantly diseased arteries if one or more coronary arteries had a stenosis >50% and with minimally diseased arteries if there was no significant stenosis (<40%) in any artery. There were no significant associations of individual polymorphisms with the risk of significant CAD. In a multivariate logistic regression analysis including cardiovascular risk factors, simultaneous presence of both LIPC -514T and CETP 405V alleles was an independent predictor of significantly diseased arteries (odds ratio = 2.04; p = 0.022). This association was not significant in women with combined genotype who had the highest HDL-cholesterol. In conclusion, the combined T allele of LIPC -514C/T and V allele of CETP I405V are associated with the risk of CAD. Further, the higher HDL-cholesterol and female gender may reduce the effect of combined genotype on CAD risk

The -514C/T Polymorphism of Hepatic Lipase Gene among Iranian Patients with Coronary Heart Disease.

BACKGROUND The T allele of the hepatic lipase (HL) C-514T polymorphism was previously found to be associated with lower plasma HL activity. Here, we examined the association between this polymorphism and plasma HDL-cholesterol concentrations in patients with coronary arteries stenosis. METHODS We studied 342 subjects undergoing coronary angiography in two groups of non CAD (n=146) and CAD (n=196). -514C→T polymorphism was determined using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). RESULTS After adjustment for age, smoking and body mass index, HDL-cholesterol concentrations were significantly higher in men with the C/T&T/T genotype than those with the C/C genotype(mean 38.6 and 34.7 respectively P=0.01). The frequency of T allele in non CAD was 0.136 and 0.226 in female and male respectively and 0.170 and 0.223 for female and male in CAD subjects. There was no difference in T allele frequency in CAD and none CAD groups in male and female (P=0.466 and 0.722 respectively). CONCLUSION -514C→T of LIPC gene have a positive effect on HDL-C concentration especially in male gender. However, no difference was determined in frequency of T allele between CAD and normal arteries subjects