Glucose-dependent insulinotropic polypeptide (GIP) and GIP receptor (GIPR) genes: An association analysis of polymorphisms and bone in young and elderly women.
BACKGROUND
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 theGIPandGIPRgenes with bone phenotypes in young and elderly women.


METHODS
Association betweenGIP(rs2291725) andGIPR(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.


RESULTS
TheGIPreceptor 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, theGIPwas associated with lower ultrasound (GG vs. AA; SOS padj= 0.021) and lower femoral neck BMD and BMC after adjusting for fat mass (padj= 0.016 and padj= 0.03). In young women, neitherGIPRnorGIPassociated with other bone phenotypes including spine trabecular bone score. In the elderly, neither SNP associated with fracture.GIPwas associated with body composition only in Peak-25;GIPRwas 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 theGIPRA-allele (β = - 6.93; padj= 0.03).


CONCLUSIONS
This first exploratory association study between polymorphisms inGIPandGIPRin 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.
Clinical and Molecular Osteoporosis Research Unit, Dept. of Clinical Science Malmö, Lund University; Dept of Orthopaedics, Skåne University Hospital Malmö, Sweden.
Gaurav
G
Garg
Clinical and Molecular Osteoporosis Research Unit, Dept. of Clinical Science Malmö, Lund University; Dept of Orthopaedics, Skåne University Hospital Malmö, Sweden.
Fiona E
FE
McGuigan
Dept of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Jitender
J
Kumar
Medical Genetics Unit, Dept. of Clinical Sciences Malmö, Lund University, Sweden.
Holger
H
Luthman
Dept of Clinical Sciences, Diabetes and Endocrinology, CRC, Lund University, Lund, Sweden; Steno Diabetes Center, Gentofte, Denmark.
Valeriya
V
Lyssenko
Clinical and Molecular Osteoporosis Research Unit, Dept. of Clinical Science Malmö, Lund University; Dept of Orthopaedics, Skåne University Hospital Malmö, Sweden.
Kristina
K
Akesson
BMD; Fat mass; GIP; GIPR; Polymorphism; Serum GIP