A functional amino acid substitution in the glucose-dependent insulinotropic polypeptide receptor (GIPR) gene is associated with lower bone mineral density and increased fracture risk
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A functional amino acid substitution in the glucose-dependent insulinotropic polypeptide receptor (GIPR) gene is associated with lower bone mineral density and increased fracture risk. / Torekov, Signe Sørensen; Harsløf, T; Rejnmark, L; Eiken, P; Jensen, J B; Herman, A P; Hansen, T; Pedersen, O; Holst, J J; Langdahl, B L.
I: The Journal of clinical endocrinology and metabolism, Bind 99, Nr. 4, 04.2014, s. E729-33.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - A functional amino acid substitution in the glucose-dependent insulinotropic polypeptide receptor (GIPR) gene is associated with lower bone mineral density and increased fracture risk
AU - Torekov, Signe Sørensen
AU - Harsløf, T
AU - Rejnmark, L
AU - Eiken, P
AU - Jensen, J B
AU - Herman, A P
AU - Hansen, T
AU - Pedersen, O
AU - Holst, J J
AU - Langdahl, B L
PY - 2014/4
Y1 - 2014/4
N2 - CONTEXT: Food ingestion decreases bone resorption, and glucose-dependent insulinotropic polypeptide (GIP) may mediate this effect. Mice overexpressing GIP have increased osteoblast activity and are rescued from age-related bone loss, whereas GIPR knockout mice have decreased cortical bone mass and compromised bone quality. Carriers of the functional variant GIPR Glu354Gln (rs1800437) have higher plasma glucose 2 hours after glucose ingestion, suggesting that the variant encoding GIPR 354Gln decreases the effect of GIP.OBJECTIVE: The objective of the study was to investigate the effect of GIPR Glu354Gln on bone mineral density (BMD) and fracture risk.DESIGN: This was a prospective, comprehensive, cohort study (number NCT00252408).PARTICIPANTS: A total of 1686 perimenopausal women were included.MAIN OUTCOME MEASURES: Dual-energy X-ray absorptiometry was performed at baseline and after 10 years. Incident fractures were recorded during the follow-up and were obtained from the Danish National Patient Registry, giving a total follow-up time of a minimum 16 years.RESULTS: After 10 years, women with the minor frequency C allele of rs1800437 (354Gln) had significantly lower BMD at the femoral neck compared with carriers of the major G-allele (CC: 0.755 ± 0.015 g/cm(2) vs CG: 747 ± 0.005 g/cm(2); GG: 0.766 ± 0.004 g/cm(2), P < .001). Correspondingly, total hip BMD was significantly lower among C allele carriers (CC: 0.881 ± 0.016 g/cm(2); CG: 0.884 ± 0.005 g/cm(2); and GG: 0.906 ± 0.004 g/cm(2), P < .001). Finally, women homozygous for the variant C allele had an increased risk (hazard ratio 1.6, confidence interval 1.0-2.6, P < .05) of nonvertebral fractures.CONCLUSION: This study demonstrates an association between a functional GIPR polymorphism Glu354Gln (rs1800437) and BMD and fracture risk. These findings further establish GIP to be involved in the regulation of bone density.
AB - CONTEXT: Food ingestion decreases bone resorption, and glucose-dependent insulinotropic polypeptide (GIP) may mediate this effect. Mice overexpressing GIP have increased osteoblast activity and are rescued from age-related bone loss, whereas GIPR knockout mice have decreased cortical bone mass and compromised bone quality. Carriers of the functional variant GIPR Glu354Gln (rs1800437) have higher plasma glucose 2 hours after glucose ingestion, suggesting that the variant encoding GIPR 354Gln decreases the effect of GIP.OBJECTIVE: The objective of the study was to investigate the effect of GIPR Glu354Gln on bone mineral density (BMD) and fracture risk.DESIGN: This was a prospective, comprehensive, cohort study (number NCT00252408).PARTICIPANTS: A total of 1686 perimenopausal women were included.MAIN OUTCOME MEASURES: Dual-energy X-ray absorptiometry was performed at baseline and after 10 years. Incident fractures were recorded during the follow-up and were obtained from the Danish National Patient Registry, giving a total follow-up time of a minimum 16 years.RESULTS: After 10 years, women with the minor frequency C allele of rs1800437 (354Gln) had significantly lower BMD at the femoral neck compared with carriers of the major G-allele (CC: 0.755 ± 0.015 g/cm(2) vs CG: 747 ± 0.005 g/cm(2); GG: 0.766 ± 0.004 g/cm(2), P < .001). Correspondingly, total hip BMD was significantly lower among C allele carriers (CC: 0.881 ± 0.016 g/cm(2); CG: 0.884 ± 0.005 g/cm(2); and GG: 0.906 ± 0.004 g/cm(2), P < .001). Finally, women homozygous for the variant C allele had an increased risk (hazard ratio 1.6, confidence interval 1.0-2.6, P < .05) of nonvertebral fractures.CONCLUSION: This study demonstrates an association between a functional GIPR polymorphism Glu354Gln (rs1800437) and BMD and fracture risk. These findings further establish GIP to be involved in the regulation of bone density.
KW - Alleles
KW - Amino Acid Substitution
KW - Bone Density
KW - Cohort Studies
KW - Female
KW - Femur Neck
KW - Fractures, Bone
KW - Gene Frequency
KW - Genetic Association Studies
KW - Humans
KW - Middle Aged
KW - Osteoporosis, Postmenopausal
KW - Receptors, Gastrointestinal Hormone
U2 - 10.1210/jc.2013-3766
DO - 10.1210/jc.2013-3766
M3 - Journal article
C2 - 24446656
VL - 99
SP - E729-33
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 4
ER -
ID: 117418185