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The role of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is under debate. We studied the association of four polymorphisms (Taq1B, I405V, R451Q and A373P) in the CETP gene with lipid profile and coronary artery disease.Four CETP polymorphisms were studied in 316 Tunisian patients undergoing coronary angiography. Patients were clinically examined and their lipid profiles were estimated. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism analysis.The 451Q allele, associated with lower high-density lipoprotein-cholesterol (HDL-C) and higher total cholesterol and apolipoprotein B (ApoB) concentrations, was also significantly associated with an increased risk of significant stenosis [odds ratio (OR) = 1.74, 95% confidence interval (CI) 1.15–2.61, P = 0.007]. The B2 allele of Taq1B polymorphism had an increase in HDL-C concentration and was associated with a decreased risk of coronary stenosis, as described earlier. It was also associated with low risk of hypoHDLaemia [OR = 0.615, 95% CI 0.377–1.002, P = 0.035]. No significant effect of different A373P and I405V alleles was found on the lipid profile and on coronary stenosis. When CETP polymorphisms were combined in haplotypes possessing R451Q, A373P, I405V, Taq1B polymorphisms, the 1112 haplotype (where 1 is the wild genotype and 2 represents carriers of the variant allele) seems to be the most protective against significant stenosis (OR = 0.71, 95% CI 0.188–0.983; P = 0.014), whereas 2111 was probably the most atherogenic, with an OR = 2.17, 95% CI 1.06–5.88; P = 0.039.The Q allele of the R451Q polymorphism was associated with decreased HDL-C, increased ApoB concentrations and increased risk of coronary stenosis. In haplotype analysis, we found that 1112 seems to be a protective haplotype, whereas 2111 has an atherogenic effect in a coronary Tunisian population.