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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Standard

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 tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Torekov, SS, Harsløf, T, Rejnmark, L, Eiken, P, Jensen, JB, Herman, AP, Hansen, T, Pedersen, O, Holst, JJ & Langdahl, BL 2014, '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', The Journal of clinical endocrinology and metabolism, bind 99, nr. 4, s. E729-33. https://doi.org/10.1210/jc.2013-3766

APA

Torekov, S. S., Harsløf, T., Rejnmark, L., Eiken, P., Jensen, J. B., Herman, A. P., ... Langdahl, B. L. (2014). 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. The Journal of clinical endocrinology and metabolism, 99(4), E729-33. https://doi.org/10.1210/jc.2013-3766

Vancouver

Torekov SS, Harsløf T, Rejnmark L, Eiken P, Jensen JB, Herman AP o.a. 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. The Journal of clinical endocrinology and metabolism. 2014 apr;99(4):E729-33. https://doi.org/10.1210/jc.2013-3766

Author

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. / 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. I: The Journal of clinical endocrinology and metabolism. 2014 ; Bind 99, Nr. 4. s. E729-33.

Bibtex

@article{ee426a7e0a504131b9b034185fdacb3b,
title = "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",
abstract = "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.",
keywords = "Alleles, Amino Acid Substitution, Bone Density, Cohort Studies, Female, Femur Neck, Fractures, Bone, Gene Frequency, Genetic Association Studies, Humans, Middle Aged, Osteoporosis, Postmenopausal, Receptors, Gastrointestinal Hormone",
author = "Torekov, {Signe S{\o}rensen} and T Harsl{\o}f and L Rejnmark and P Eiken and Jensen, {J B} and Herman, {A P} and T Hansen and O Pedersen and Holst, {J J} and Langdahl, {B L}",
year = "2014",
month = "4",
doi = "10.1210/jc.2013-3766",
language = "English",
volume = "99",
pages = "E729--33",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Oxford University Press",
number = "4",

}

RIS

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