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17.07.2018 | Original Article

LRP5 gene polymorphisms and radiographic joint damage in rheumatoid arthritis patients

verfasst von: M. Bernardes, C. Durães, A. Oliveira, M. J. Martins, R. Lucas, L. Costa, J. G. Pereira, I. Ramos, J. C. Machado, F. Simões-Ventura

Erschienen in: Osteoporosis International | Ausgabe 10/2018

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Abstract

Summary

Rheumatoid arthritis (RA) is characterized by increased bone resorption and impaired bone formation. Osteoblast function is regulated by the canonical LRP5/Wnt/β-catenin pathway. Bone mineral density and RA joint destruction are partially inherited. In line with this, we found significant associations between LRP5 SNPs (p.A1330V, p.N740N, p.V667M) and RA radiographic damage severity.

Introduction

Increased bone resorption and impaired bone formation characterize rheumatoid arthritis (RA). Canonical Wnt/β-catenin pathway, signalled by lipoprotein receptor-related protein-5 (LRP5), regulates osteoblast function. Since bone mineral density (BMD) and RA joint destruction are partially inherited, we studied their association with LRP5 single nucleotide polymorphisms (SNPs).

Methods

Clinical data and peripheral blood for biomarkers assessment and LRP5 genotyping were collected from 208 RA patients. Hands and feet X-rays were scored [modified Sharp/van der Heijde Score (SHS), joint space narrowing (JSN), and erosion scores]. Lumbar spine, total left proximal femur, and left hand BMD were assessed by dual-energy X-ray absorptiometry (DXA).

Results

TT genotypes for p.A1330V and p.N740N LRP5 SNPs associated with total SHS, erosion score, and hands erosion score; the same for p.A1330V with feet JSN score and p.N740N with hands total score. AG genotype for p.V667M associated with sclerostin and hands JSN score. Femoral BMD associated with TC genotype for p.N740N. Multiple test correction precluded a few of these associations. Among V667M-N740N-A1330V haplotypes: GTT associated with higher feet JSN score (OR = 3.80; p = 0.016) and ATT with higher JSN score (OR = 4.60; p = 0.032), hands total score (OR = 5.65; p = 0.022), and total SHS (OR = 6.74; p = 0.024).

Conclusion

Significant associations between LRP5 SNPs (p.A1330V, p.N740N, and p.V667M) and the severity of radiographic damage reinforce the evidence of bone destruction heritability in RA.

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Titel: LRP5 gene polymorphisms and radiographic joint damage in rheumatoid arthritis patients
verfasst von: M. Bernardes
C. Durães
A. Oliveira
M. J. Martins
R. Lucas
L. Costa
J. G. Pereira
I. Ramos
J. C. Machado
F. Simões-Ventura
Publikationsdatum: 17.07.2018
Verlag: Springer London
Erschienen in: Osteoporosis International / Ausgabe 10/2018
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-018-4625-3

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LRP5 gene polymorphisms and radiographic joint damage in rheumatoid arthritis patients

Abstract

Summary

Introduction

Methods

Results

Conclusion

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