Genome-wide association study identifies genetic variants which predict the response of bone mineral density to teriparatide therapy.
Ann Rheum Dis
; 82(7): 985-991, 2023 07.
Article
en En
| MEDLINE
| ID: mdl-36941031
ABSTRACT
OBJECTIVES:
Teriparatide (TPTD) is an effective treatment for osteoporosis but the individual response to therapy is variable for reasons that are unclear. This study aimed to determine whether the response to TPTD might be influenced by genetic factors.METHODS:
We searched for predictors of the response of bone mineral density (BMD) to TPTD using a two-stage genome-wide association study in 437 patients with osteoporosis from three referral centres. Demographic and clinical data including the response of BMD to treatment at the lumbar spine and hip were extracted from the medical records of each participant.RESULTS:
Allelic variation at rs6430612 on chromosome 2, close to the CXCR4 gene was associated with the response of spine BMD to TPTD at a genome wide significant level (p=9.2×10-9 beta=-0.35 (-0.47 to -0.23)). The increase in BMD was almost twice as great in AA homozygotes at rs6430612 as compared with GG homozygotes with intermediate values in heterozygotes. The same variant was also associated with response of femoral neck and total hip BMD (p=0.007). An additional locus on chromosome 19 tagged by rs73056959 was associated with the response of femoral neck BMD to TPTD (p=3.5×10-9, beta=-1.61 (-2.14 to -1.07)).CONCLUSIONS:
Genetic factors influence the response to TPTD at the lumbar spine and hip with a magnitude of effect that is clinically relevant. Further studies are required to identify the causal genetic variants and underlying mechanisms as well as to explore how genetic testing for these variants might be implemented in clinical practice.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Osteoporosis
/
Osteoporosis Posmenopáusica
/
Conservadores de la Densidad Ósea
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Ann Rheum Dis
Año:
2023
Tipo del documento:
Article
País de afiliación:
Reino Unido