The goal of our study was to explore the significant association between a non-protein coding single nucleotide polymorphism (SNP) rs4977574 of CDKN2BAS gene and coronary heart disease (CHD). A total of 590 CHD cases and 482 non-CHD controls were involved in the present association study. A strong association of rs4977574 with CHD was observed in females (genotype: p = 0.002; allele: p = 0.002, odd ratio (OR) = 1.57, 95% confidential interval (CI) = 1.18-2.08). Moreover, rs4977574 was more likely to be a risk variant of CHD under the recessive model in females ((2) = 10.29, p = 0.003, OR = 2.14, 95% CI = 1.31-2.77). A breakdown analysis by age had shown that there was an 87% increased risk of CHD for females younger than 65 years (genotype: (2) = 14.64, degrees of freedom (df) = 2, p = 0.0002; allele: (2) = 11.31, df = 1, p = 0.0008, OR = 1.87, 95% CI = 1.30-2.70). Similar observation was also found in males younger than 65 years (genotype: (2) = 8.63, df = 2, p = 0.04; allele: (2) = 7.55, df = 1, p = 0.006, OR = 1.45, 95% CI = 1.11-1.90). p values were adjusted by age, sex, smoking, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). Meta-analysis of 23 studies among 36,452 cases and 39,781 controls showed a strong association between rs4977574 and the risk of CHD (p < 0.0001, OR = 1.27, 95% CI = 1.22-1.31).