Cellular cholesterol homeostasis is controlled by the sterol-regulatory element binding transcription factors (SREBFs) that are activated by an SREBF cleavage-activating protein (SCAP). SREBF-2 1784G > C single nucleotide polymorphism (SNP, rs2228314) and SCAP 2386A > G variant (rs12487736) are associated with early onset myocardial infarction (MI) and sudden cardiac death in middle-aged men. We investigated whether these two SNPs are determinants of premature coronary artery disease (CAD) in a Chinese population. We studied 431 consecutive patients, including 197 with coronary stenosis ≥50% or previous MI and 234 controls without documented CAD (males <55 years and females <65 years). All subjects were genotyped for two SNPs by using the ligase detection reaction method. The three genotypes GG, GC, and CC were present in rs2228314 and two genotypes AA and AG in rs12487736. No gender-specific differences were found in genotype distribution and allele frequencies of these two SNPs between patients with and without CAD. The biochemical and clinical risk factors among participants were not influenced by variants at rs2228314. Logistic regression did not detect the association of these two SNPs with premature CAD, nor did there exist any association of these two SNPs among groups of patients with 0, 1, 2, and 3-vessel disease (all P > 0.05). We could not identify any association between these two SNPs and premature CAD or extent of coronary lesions in a Chinese population.