Genetic Variability of the Glucose-Dependent Insulinotropic Peptide Gene Is Involved in the Premature Coronary Artery Disease in a Chinese Population with Type 2 Diabetes

BACKGROUND: Glucose-dependent insulinotropic polypeptide (GIP) is closely related to diabetes and obesity, both of which are confirmed to increase the risk of coronary artery disease (CAD). Our study aimed to investigate whether the polymorphisms in GIP genes could affect the risk of cardiovascular disease in type 2 diabetic patients in the Chinese Han population. METHODS: We selected and genotyped two haplotype-tagging single nucleotide polymorphisms (tag-SNPs) (rs2291725 C>T, rs8078510 G>A) of GIP gene based on CHB data in HapMap Phase II database (r(2) < 0.8). The case-control study of Chinese Han population involved 390 diabetic patients with CAD as positive group and 276 diabetic patients without CAD as control group. Allele and genotype frequencies were compared between the two groups. RESULTS: In dominant inheritance model, the carriers of T/T or T/C had a lower risk of CAD (OR = 0.635, 95% CI = 0.463–0.872, p = 0.005), even after adjustment other CAD risk factors (gender, age, BMI, smoking status, dyslipidemia, hypertension history, and diabetic duration) (OR′ = 0.769, 95% CI′ = 0.626–0.945, p′ = 0.013). The allele A at rs8078510 was associated with decreased risk of CAD (OR = 0.732, p = 0.039). p = 0.018 in subgroup analysis, individuals with higher BMI (≥24 kg/m(2)) had increased risk for CAD when carrying C/C at rs2291725 (OR′ = 1.291, 95% CI′ = 1.017–1.639, p′ = 0.036). In age < 55 men and age < 65 women, the carriers of allele C at rs2291725 had a higher risk of CAD than noncarriers (OR = 1.627, p = 0.015). Carriers of allele G in rs8078510 had higher susceptibility to CAD (OR = 2.049, 95% = CI 1.213–3.463, p = 0.007). p = 0.004; in addition, allele G in rs8078510 would bring higher CAD risk to the carriers who ever smoked (OR = 1.695, 95% CI = 1.080–2.660, p = 0.021). CONCLUSION: The genetic variability of GIP gene is associated with CAD and it may play a role in the premature CAD in the Chinese Han population with type 2 diabetes.