Association of variants in gastric inhibitory polypeptide receptor gene with impaired glucose homeostasis in obese children and adolescents from Berlin

Abstract

OBJECTIVE: In the past 20 years, obesity has become a major health problem due to associated diseases like type 2 diabetes mellitus. The gastric inhibitory polypeptide receptor (GIPR) modulates body weight and glucose homeostasis and, therefore, represents an interesting candidate gene for obesity and the comorbidity impaired glucose homeostasis. Recently, a GIPR variation was found to be associated with impaired insulin response in humans. In this study, we screened the GIPR gene for mutations and examined the association between three single-nucleotide polymorphisms (SNPs; rs8111428, rs2302382, rs1800437) and childhood obesity, as well as impaired glucose homeostasis. METHODS: The coding region of the GIPR was screened for mutations by direct sequencing. We genotyped three known SNPs in 2280 healthy normal weight (1696) and obese (584) children and adolescents. Genotyping was performed using the SNaPshot protocol, the iplex, and matrix-assisted laser desorption ionization time-of-flight spectrometry technique. Obesity was defined by a body mass index SDS above 2; homeostatic model assessment was calculated. RESULTS: No evidence for an association was found between the SNPs and the obesity phenotype. Significant association was found between the minor allele C of the SNP rs1800437 and elevated homeostasis model of insulin resistance values (P=0.001). No further sequence variations in the GIPR were found to be associated with childhood obesity. CONCLUSION: Variations of the GIPR sequence are not associated with childhood obesity. This study points to a potential role for rs1800437 in glucose homeostasis. Further studies are necessary to confirm these results.