Dyslipidemia, especially hypercholesterolemia, is a major risk factor of coronary heart disease (CHD). The insulin induced gene 1 (INSIG1) and insulin induced gene 2 (INSIG2) encode two proteins which mediate feedback control of cholesterol synthesis. We conducted a case-control study to investigate whether the common variants in INSIG genes were associated with CHD in Chinese Han population. Three single nucleotide polymorphisms (SNPs) of the INSIG1 gene and four SNPs of the INSIG2 gene were chosen as haplotype-tagging SNPs (htSNPs) and genotyped in 853 patients with CHD and 948 unrelated control subjects. Haplotype analysis showed that the haplotype Hap4 (TTA) of the INSIG1 gene significantly increased the risk of CHD (adjusted odds ratio [OR]1.59, 95% confidence interval [CI] 1.22-2.06, p = 0.0006), while the haplotype Hap3 (TGA) significantly decreased the risk of CHD (adjusted OR 0.74, 95%CI 0.60-0.92, p = 0.006) compared with the reference haplotype Hap1 (GGA). No significant associations were found between polymorphisms of INSIG2 gene and CHD. In addition, the single polymorphism analysis showed that rs9769826 of the INSIG1 gene was associated with glucose in controls. The G-allele (minor allele) carriers had higher glucose level (5.74 +/- 2.03 mM) than AA genotype carriers (5.45 +/- 1.37 mM, p = 0.015). The present study indicated that the INSIG1 gene, but not the INSIG2 gene, was associated with CHD in the Chinese population.