The INSIG1 gene, not the INSIG2 gene, associated with coronary heart disease: tagSNPs and haplotype-based association study

Dyslipidemia, especially hypercholesterolemia, is a mal. or 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 INSIG 1 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 INSIG I 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 Hap 1 (GGA). No significant associations were found between polymorphisms of INSIG2 gene and CHD. In addition,the single polymorphism analysis showed that rs9769826 of the INSIG 1 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 +/- 1.37mM,p=0.015).The present study indicated that the INSIG I gene, but not the INSIG2 gene, was associated with CHD in the Chinese population.