Objectives: Apolipoprotein M (apoM) is important for the formation of pre-beta-high-density lipoprotein (HDL) and cholesterol efflux in macrophages. It is demonstrated that single-nucleotide polymorphism (SNP) T-778C of apoM gene is related to type 2 diabetes in Han Chinese. In the present study. we investigated the possible association of apoM polymorphism in relation to coronary artery disease (CAD) in Han Chinese. Design and methods: This case-controlled study consisted of 118 CAD patients who were diagnosed angiographically to have at least 30% stenosis, and 255 unrelated subjects who were used as control. ApoM gene polymorphisim in the proximal promoter region was analyzed by PCR-RFLP and serum lipid levels were also measured. Results: It is indicated that CAD patients had increased frequency of C allele on apoM T-778C compared to the controls (14.8% vs. 6.9%, P=0.0008). Multivariable logistic regression analysis indicated that odds ratios (ORs) for all subjects with apoM CC+CT genotypes and C allele were 1.9 (95% CI= 1.1-2.9, P < 0.0001) and 1.9 (95% CI= 1.3-3.2 P < 0.0001), respectively. The plasma total cholesterol (TC) levels were significantly higher in individuals with CC or CT genotype than those with TT genotype in both CAD patients and controls. Conclusions: The present findings suggest that the C allele at nucleoticle - 778 in the apoM gene is a risk factor for genetic susceptibility to CAD and is also associated with TC levels in Han Chinese. C) 2007 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.