Pathogenetic significance of single nucleotide polymorphisms in the gastric inhibitory polypeptide receptor gene for the development of carbohydrate metabolism disorders in obesity

Abstract

Aim. To investigate the association of the GIPR gene polymorphisms rs2302382 and rs8111428 with increased risk of type 2 diabetes mellitus and abdominal obesity. Materials and methods. The study involved 163 patients with abdominal obesity (BMI, 39.5 ± 8.3 kg/m2; age, 44.7 ± 8.9 years; men, 61; women, 102), 72 with type 2 diabetes mellitus (BMI, 43.70 ± 9.32 kg/m2; age, 46.5 ± 10.1 years; men, 29; women, 43) and 91 patients without carbohydrate metabolism disorders (BMI, 36.13 ± 6.72 kg/m2; age, 43.93 ± 8.35 years; men, 32; women 59). The control group comprised 109 relatively healthy volunteers (BMI, 22.6 ± 2.7 kg/m2; age, 39.5 ± 7.6 years; men, 66; women, 43). Genotypes were analysed by real-time PCR and serum insulin and C-peptide levels were evaluated by ELISA. Results. The AA genotype in the rs2302382 polymorphism of GIPR was associated with an increased risk for type 2 diabetes mellitus in abdominal obesity and the CA genotype was associated with a reduced risk. In individuals with abdominal obesity and type 2 diabetes mellitus carrying the CA genotype in rs2302382 polymorphism of GIPR, serum insulin and C-peptide levels were elevated to 56.27 mU/L (55.49-58.41 mU/L) and 2.04 ng/ml (1.37-2.85 ng/ml), respectively (p < 0.05). In obese patients with the same genotype and without type 2 diabetes, serum insulin levels and C-peptide levels were 22.73 mU/L (19.07-25.76 mU/L) and 0.73 ng/ml (0.53-1.03 ng/ml), respectively (p < 0.05). The GIPR rs8111428 polymorphism was not associated with increased risk of type 2 diabetes mellitus in obesity for any of the groups examined. Conclusion. Serum insulin and C-peptide levels were increased in patients with abdominal obesity who were carriers of the CA genotype in the rs2302382 polymorphism of GIPR, which is associated with a decreased risk of type 2 diabetes mellitus in obesity compared with the CC genotype.