Obesity Variants in the GIPR Gene Are not Associated With Risk of Fracture or Bone Mineral Density.
J Clin Endocrinol Metab
; 109(8): e1608-e1615, 2024 Jul 12.
Article
em En
| MEDLINE
| ID: mdl-38118020
ABSTRACT
CONTEXT It is not clear if antagonizing the GIP (glucose-dependent insulinotropic polypeptide) receptor (GIPR) for treatment of obesity is likely to increase the risk of fractures, or to lower bone mineral density (BMD) beyond what is expected with rapid weight loss. OBJECTIVE:
The objective of this study was to investigate the risk of fracture and BMD of sequence variants in GIPR that reduce the activity of the GIP receptor and have been associated with reduced body mass index (BMI).METHODS:
We analyzed the association of 3 missense variants in GIPR, a common variant, rs1800437 (p.Glu354Gln), and 2 rare variants, rs139215588 (p.Arg190Gln) and rs143430880 (p.Glu288Gly), as well as a burden of predicted loss-of-function (LoF) variants with risk of fracture and with BMD in a large meta-analysis of up to 1.2 million participants. We analyzed associations with fractures at different skeletal sites in the general population any fractures, hip fractures, vertebral fractures and forearm fractures, and specifically nonvertebral and osteoporotic fractures in postmenopausal women. We also evaluated associations with BMD at the lumbar spine, femoral neck, and total body measured with dual-energy x-ray absorptiometry (DXA), and with BMD estimated from heel ultrasound (eBMD).RESULTS:
None of the 3 missense variants in GIPR was significantly associated with increased risk of fractures or with lower BMD. Burden of LoF variants in GIPR was not associated with fractures or with BMD measured with clinically validated DXA, but was associated with eBMD.CONCLUSION:
Missense variants in GIPR, or burden of LoF variants in the gene, are not associated with risk of fractures or with lower BMD.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Receptores dos Hormônios Gastrointestinais
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Densidade Óssea
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Fraturas Ósseas
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Obesidade
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Clin Endocrinol Metab
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Islândia