Despite all evidence for the involvement and importance of GIPR in obesity, until now few studies analysed variants in GIPR and their risk for obesity. Some studies involving the non-synonymous variant rs1800437 did not reveal association with increased BMI [21,39] or to non-insulin-dependent diabetes [39,40]. However, in one study, C-peptide concentrations in serum of homozygous individuals for the C-allele (minor allele) of rs1800437 were significantly decreased (14%) after fasting [39]. Additionally, association with lower cholesterol levels was found in heterozygous individuals with CVD [21]. Thus, the results of both studies (Lower C-peptide concentrations [39] and lower cholesterol levels [21]) are in line with our case-control study where the C-allele was more frequent in controls than in cases. Additionally, in our German obesity families, we found a trend of the G-allele (major allele) to be more frequently transmitted to severely obese offspring (p = 0.076). Taken together, these results suggest an association of the G-allele of rs1800437 with obesity. If a dysfunctional GIPR receptor leads to a lower fat mass we have to assume that obesity would be associated with gain
