Polymorphisms in the Glucagon-Like Peptide 1 Receptor (GLP-1R) Gene Are Associated with the Risk of Coronary Artery Disease in Chinese Han Patients with Type 2 Diabetes Mellitus: A Case-Control Study

BACKGROUND: Glucagon-like peptide 1 (GLP-1) bestows protective effects upon the cardiovascular system through direct cardiovascular interactions or by improvements to metabolic function. Both these effects are thought to be at least partly mediated by the GLP-1 receptor (GLP-1R). This case-controlled study investigated whether polymorphisms in the GLP-1R gene affect the risk of cardiovascular disease in type 2 diabetic patients in the Chinese Han population. METHODS: Eleven haplotype-tagging single nucleotide polymorphisms (SNPs), distributed across 22 kb of the 39 kb GLP-1R gene, were selected and genotyped in diabetic patients from a Chinese Han population. Patients were classified based on the severity of coronary artery stenosis. Coronary artery stenosis was ≥50% in 394 patients (coronary artery disease- (CAD-) positive group), and coronary artery stenosis was <50% in 217 patients (control group). Allele and genotype frequencies were compared between the two groups at all 11 SNPs. RESULTS: When considered in recessive inheritance mode, patients with the GG genotype at rs4714210 had a lower CAD risk than patients with other genotypes (OR = 0.442, 95% CI = 0.258–0.757, p = 0.002), even when other known CAD risk factors were taken into account (OR(a) = 0.440, 95% CI(a) = 0.225–0.863, p (a) = 0.017). In additive inheritance mode, GG genotype carriers at rs4714210 exhibited a lower risk of CAD than AA carriers (OR(a) = 0.475, CI(a) = 0.232–0.970, p (a) = 0.041). CONCLUSION: In type 2 diabetic patients from a Han Chinese population, some variations in the GLP-1R gene were associated with a lower risk of developing CAD.