In contrast, the locus near GIPR, which encodes a receptor of gastric inhibitory polypeptide (GIP), suggests a role for peripheral biology in obesity. GIP, which is expressed in the K cell of the duodenum and intestine, is an incretin hormone that mediates incremental insulin secretion in response to oral intake of glucose. The variant associated with BMI is in strong LD (r2 = 0.83) with a missense SNP in GIPR (rs1800437, Glu354Gln) that has recently been shown to influence the glucose and insulin response to an oral glucose challenge 21. Although no human phenotype is known to be caused by mutations in GIPR, mice with disruption of Gipr are resistant to diet-induced obesity32. The association of a variant in GIPR with BMI suggests that there may be a link between incretins/insulin secretion and body weight regulation in humans as well.
