The association of the single nucleotide polymorphism 301T>C in the coding region of the acylation-stimulating protein (ASP) gene with coronary heart disease (CHD) was investigated in the Uygur (385 CHD patients and 483 control subjects) and Han (390 CHD patients and 439 control subjects) populations of China. The frequency of the CC and CT genotypes was significantly higher in patients with CHD compared to the control group (55.3 vs 46.2%, P = 0.001) in the Uygur population, but in the Han population, the frequency was significantly higher in the control group (51.7 vs 24.4%, P < 0.001). In addition, the C allele was significantly associated with CHD in the Uygur population (C allele: 33.8 vs 26.2%, T allele: 66.2 vs 73.8%; P = 0.004) and in the Han population (C allele: 14.5 vs 30.3%, T allele: 85.5 vs 69.7%; P < 0.001). The CC genotype was independently associated with increased risk of coronary artery disease when adjusted for other cardiovascular risk factors [odds ratio (OR) = 2.189, 95% confidence interval (CI) = 1.251-3.830, P = 0.001] in the Uygur population, but was a protective factor for CHD in the Han population (OR = 0.373, 95%CI = 0.187-0.745, P = 0.005). In conclusion, the 301T>C polymorphism of the ASP gene that influences the serum triglycerides level in the Uygur population, is associated with the development of CHD, and the CC genotype might be a risk factor of CHD.