Cholesteryl ester transfer protein (CETP) is a key participant in the reverse transport ofcholesterol from the peripheral tissues to the liver. To understand the role that CETP gene plays in thepathogenesis of coronary heart disease (CHD), the promoter region, all 16 exons and adjacent intronicregions of CETP gene were screened for single nucleotide polymorphisms (SNPs) in 203 CHD patients and209 controls by a combination of PCR, denaturing high performance liquid chromatography (DHPLC),molecular cloning, and DNA sequencing. A novel missense mutation in the CETP gene was identified. Thismutation (L296Q) was a T-to-A conversion at codon 296 of exon 10 which replaced the codon for leucine(CTG) with the codon for glutamine (CAG). Association study revealed that L296Q mutation was associatedwith CHD with a significantly higher mutant allele frequency in the CHD patients than that in the controls (0.160 vs. 0.091,x2= 9.014, P = 0.003), and that the odds ratio for the development of CHD was 1.83 for the296Q allele carriers relative to 296LL homozygotes. Statistical analyses demonstrated that the mutant 296Q allelecarrier patients displayed significantly higher total cholesterol (TC) and low density lipoprotein cholesterol(LDL-C) concentrations than non-carrier patients. The results of the present study suggest that the L296Qmutation is related to CHD, and the identification of new mutations in the CETP gene will afford the oppor-tunity to investigate the relationship between CETP gene and CHD.