Six lipoprotein lipase gene polymorphisms, lipid profile and coronary stenosis in a Tunisian population.

Lipoprotein lipase (LPL) is the rate-limiting enzyme in the hydrolysis of triglyceride-rich lipoprotein particles (Chylomicrons and very-low-density lipoprotein). LPL polymorphisms' effects on lipids and coronary artery disease are controversial among studies and populations. Our aim was to study the association between six polymorphisms, haplotypes and significant coronary stenosis (SCS), disease severity and lipid parameters in Tunisian patients. LPL PvuII, 93 T/G, 188 G/E, HindIII, N291S and D9N polymorphisms were analyzed in 316 patients who underwent coronary angiography. Assessment of coronary angiograms identified SCS as the presence of stenosis >50 % in at least one major coronary artery. The stenosis severity was determined by using Gensini score and vessels number. A significant association of SCS with TT of the HindIII polymorphism was showed (odds ratio (OR): 2.84, 95 % CI, 1.19-7.40, p = 0.017) and TG (OR: 1.77, 95 % CI, 1.99-2.82, p = 0.033). The mutated HindIII genotype was significantly associated with increased TG and ApoB/ApoA-I ratio and with decreased HDL-C. Haplotype analysis showed that OR of SCS associated with the CTGTAG haplotype was 2.12 (95 % CI 1.05-4.25, p = 0.032) and with CGGGAA was 0.71 (95 % CI 0.26-1.95, p = 0.022) compared to the CTGTAA. Significant difference in Gensini score was observed among HindIII genotype and haplotypes. A significant association between the mutated genotype of HindIII polymorphism and decreased HDL-C level and increased ApoB/ApoA-I ratio and TG level was showed. Our results suggest that HindIII and D9N polymorphisms and CTGTAG haplotype seem to be considered as marker of predisposition to coronary stenosis. In another hand, HindIII and haplotypes were related to stenosis severity.

Associations between common polymorphisms of adenosine triphosphate-binding cassette transporter A1 and coronary artery disease in a Tunisian population.

BACKGROUND: The adenosine triphosphate-binding cassette transporter A1 (ABCA1) protein plays an important role in the first step of the reverse cholesterol transport system. AIMS: We studied the association of four polymorphisms in the ABCA1 gene (G1051A, G2706A, G2868A and -565C/T) with lipid profile and coronary artery disease. METHODS: Overall, 316 Tunisian patients underwent coronary angiography. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism analysis. Lipid and apolipoprotein concentrations were measured. RESULTS: Only carriers of the G2706A allele were associated with a decreased risk of significant stenosis (odds ratio [OR] 0.66, 95% confidence interval [CI] 0.22-0.92, p = 0.029), without pronounced effects on high-density lipoprotein (HDL) cholesterol. This protective effect was significant in smokers and diabetes. Carriers of the G1051A allele were associated only with increased concentrations of HDL cholesterol (p = 0.032). G2868A and -565C/T did not show any association with lipids or risk of significant stenosis. When ABCA1 polymorphisms were combined in haplotypes possessing G1051A, G2706A, G2868A and -565C/T, (AAGC) seemed to be most protective against significant stenosis (OR 0.5, 95% CI 0.29-0.96, p = 0.048) whereas (GGAT) was probably the most atherogenic (OR 1.26, 95% CI 1.03-1.56, p = 0.025). CONCLUSION: Only the G2706A allele seems to be associated with a reduced risk of significant stenosis without important modification of HDL-cholesterol concentration, and appears to be more protective for smokers and diabetic patients. We found that (AAGC) seems to be a protective haplotype whereas (GGAT) has an atherogenic effect in a Tunisian population.

5' ins/del and 3' VNTR polymorphisms in the apolipoprotein B gene in relation to lipids and coronary artery disease.

BACKGROUND: Studies that considered apolipoprotein B (APOB) gene polymorphisms as risk factors for coronary artery disease (CAD) have reported conflicting results. We sought to analyze the association between 5' ins/del and 3' VNTR polymorphisms of APOB, lipid parameters and CAD risk. METHODS: We recruited 251 patients with CAD, documented by coronary angiography, and 94 controls. Genotyping was performed by PCR. Lipids and apolipoproteins were measured. RESULTS: 5' ins/del (ins/ins, ins/del, del/del) and 3' VNTR (LL, SS, LS) polymorphism frequencies were significantly (p<0.05) different between controls and CAD patients. LL and del/del were significantly associated with higher levels of apolipoprotein B (apoB), total cholesterol/high-density lipoprotein cholesterol ratio and apoB/apoA-I ratio (p<0.05) and with increased risk of CAD. The odds ratio for significant coronary stenosis associated with del/del was 3.2 (95% CI 1.6-36.42) (p=0.032) and with LL was 2.2 (95% CI 1.1-5.1) (p=0.042). CONCLUSIONS: The two polymorphisms exert an impact on lipid levels and contribute to the susceptibility to the development of CAD.

Association of the cholesteryl ester transfer protein Taq1 B2B2 genotype with higher high-density lipoprotein cholesterol concentrations and lower risk of coronary artery disease in a Tunisian population.

BACKGROUND: The role of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is undergoing debate. AIMS: In this prospective study, we sought to explore the role of the CETP Taq1B variant in coronary artery disease risk, and its association with plasma lipid and apolipoprotein concentrations. METHODS: DNA was extracted from 316 patients undergoing coronary angiography. The Taq1B polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis. Lipid and apolipoprotein concentrations were measured by enzymatic and nephelometric assays. RESULTS: In our study population, the B2 allele frequency was 0.29. B2 allele carriers had a significantly higher high-density lipoprotein cholesterol (HDL-C) concentration than those with the B1B1 genotype (1.041+/-0.294 versus 0.995+/-0.277; p=0.039). After adjusting for age, sex, smoking status, diabetes, hypertension and dyslipidaemia, the odds ratio (OR) for significant stenosis associated with the B2 allele was 0.82 (95% confidence interval (CI) 0.60-0.97; p=0.039), suggesting that the B2 allele is associated with an 18% lower risk of significant stenosis. This protective effect seemed to be more significant in male nonsmokers (38% lower risk; OR 0.62, 95% CI 0.29-0.92; p=0.029). No significant protective effects were observed in women or male smokers. CONCLUSION: Our data suggest that the B2 allele is associated with higher concentrations of HDL-C, which confer a protective effect with regard to coronary atherosclerosis. This effect seems to be more significant in men than in women and in nonsmokers than in smokers.