The gene polymorphisms of insulin degrading enzyme (IDE) are associated with the risk of coronary heart disease in Chinese Han population

Objectives: Altered insulin degrading enzyme function leads to toxic amyloidand insulin aggregates, inflammation, and atherosclerosis. We hypothesized that gene polymorphisms of insulin degrading enzyme (IDE) are associated with the development of coronary heart disease (CHD). Methods: In this case-control study, 231 CHD patients and 200 non-CHD controls were selected according to the coronary angiography (CAG) results. Sequenom's MassARRAY system was used to genotype 5 IDE gene TagSNPs, namely rs1887922, rs2149632, rs6583817, rs4646954, and rs3758505. The frequencies of the alleles, genotypes, and haplotypes of these TagSNPs were compared between the CHD and control groups. Results: The rs1887922, rs2149632, and rs4646954 were significantly associated with the risk of developing CHD (P<0.05). Haplotype analysis of rs1887922-rs2149632-rs6583817-rs4646954-rs3758505 showed that the CTCGT haplotype increased the risk of developing CHD (P<0.001; OR=3.429, 95% CI: 1.816-6.475), while the TCCGT reduced the risk (P=0.020; OR=0.708, 95% CI: 0.530-0.947). In addition, the rs1887922 C allele was associated with reduced hepatic insulin clearance (HIC) (P<0.001), decreased glycosylated hemoglobin (HbA1c) (P=0.032), and increased plasma insulin concentration (P=0.023). Conclusions: IDE gene polymorphisms are closely associated with the risk of developing CHD in Chinese Han population.