Glucose-dependent insulinotropic polypeptide (<i>GIP</i>) and GIP receptor (<i>GIPR</i>) genes: An association analysis of polymorphisms and bone in young and elderly women.

Abstract

The gastro-intestinal hormone glucose-dependent insulinotropic polypeptide (GIP) potentiates glucose-induced insulin secretion, with bone anabolic effects through GIP receptor (GIPR) in animal models. We explore its potential in humans by analyzing association between polymorphisms (SNPs) in the <i>GIP</i> and <i>GIPR</i> genes with bone phenotypes in young and elderly women. Association between <i>GIP</i> (rs2291725) and <i>GIPR</i> (rs10423928) and BMD, bone mineral content (BMC), bone microarchitecture, fracture and body composition was analyzed in the OPRA (75y, n = 1044) and PEAK-25 (25y; n = 1061) cohorts and serum-GIP in OPRA. The <i>GIP</i> receptor AA-genotype was associated with lower ultrasound values in young women (BUA p = 0.011; SI p = 0.030), with no association to bone phenotypes in the elderly. In the elderly, the <i>GIP</i> was associated with lower ultrasound (GG vs. AA; SOS p_adj = 0.021) and lower femoral neck BMD and BMC after adjusting for fat mass (p_adj = 0.016 and p_adj = 0.03). In young women, neither <i>GIPR</i> nor <i>GIP</i> associated with other bone phenotypes including spine trabecular bone score. In the elderly, neither SNP associated with fracture. <i>GIP</i> was associated with body composition only in Peak-25; <i>GIPR</i> was not associated with body composition in either cohort. Serum-GIP levels (in elderly) were not associated with bone phenotypes, however lower levels were associated with the <i>GIPR</i> A-allele (β = - 6.93; p_adj = 0.03). This first exploratory association study between polymorphisms in <i>GIP</i> and <i>GIPR</i> in relation to bone phenotypes and serum-GIP in women at different ages indicates a possible, albeit complex link between glucose metabolism genes and bone, while recognizing that further studies are warranted.