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A CD40 variant is associated with systemic bone loss among patients with rheumatoid arthritis

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Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Objectives

Little is known about genes predisposing to systemic bone loss (SBL) in rheumatoid arthritis (RA). Therefore, we examined the association between SBL and variants of genes playing a critical role in both immune response and bone homeostasis among patients with RA.

Methods

IRAK-1 rs3027898, IRAK-2 rs3844283, IRAK-2 rs708035, IFIH1 rs1990760, CD40 rs48104850, TNFAIP3 rs2230926, and miR146-a rs2910164 were genotyped in 176 adult RA patients. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA).

Results

Low BMD was observed in 116 (65.9%) patients. Among them, 60 (34.1%) had low femoral neck (FN) Z score, 72 (40.9%) had low total femur (TF) Z score, and 105 (59.6%) had low lumbar spine (LS) Z score. Among all the SNPs assessed, only CD40 rs4810485 was found to be associated with reduced TF Z score with the CD40 rs4810485 T allele protecting against reduced TF Z score (OR = 0.40, 95% CI = 0.23–0.68, p = 0.0005). This association was confirmed in the multivariate logistic regression analysis (OR = 0.31, 95% CI = 0.16–0.59, p = 3.84 × 10−4). Moreover, median FN BMD was reduced among RA patients with CD40 rs4810485 GG genotype compared to RA patients harbouring CD40 rs4810485 TT and GT genotypes (0.788 ± 0.136 versus 0.826 ± 0.146 g/cm2, p = 0.001). IRAK-1 rs3027898, IRAK-2 rs3844283, rs708035, IFIH rs1990760, TNFAIP3 rs2230926, and miR146-a rs2910164 were not found to be associated with SBL.

Conclusion

This study for the first time ever demonstrated an association between a CD40 genetic variant and SBL among patients with RA.

Key Points

• CD40 rs4810485 GG genotype is associated with decreased BMD among patients with RA.

• CD40 rs4810485 might serve as a genetic marker for SBL in RA.

• CD40 genetic variations might be integrated in future development of more effective therapeutic interventions for prevention of SBL in RA.

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Acknowledgements

This study was supported by the college of Medicine Research center, Deanship of Scientific Research, King Saud University, Riyadh, Saudi Arabia.

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Authors and Affiliations

  1. Department of Pathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia

    Rim Sghiri, Zahid Shakoor & Adel Almogren

  2. Immunogenetics Unit, Faculty of Medicine, University of Sousse, Sousse, Tunisia

    Hana Benhassine, Meriem Ghozzi, Foued Slama, Nadia Idriss, Zeineb Benlamine & Ramzi Zemni

  3. Department of Rheumatology, Farhat Hached Hospital, Sousse, Tunisia

    Khadija Baccouche, Sarra Jriri & Elyes Bouajina

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  1. Rim Sghiri
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Sghiri, R., Benhassine, H., Baccouche, K. et al. A CD40 variant is associated with systemic bone loss among patients with rheumatoid arthritis. Clin Rheumatol 41, 1851–1858 (2022). https://doi.org/10.1007/s10067-021-05998-9

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