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. 2022 Jun;41(6):1851-1858.
doi: 10.1007/s10067-021-05998-9. Epub 2022 Feb 2.

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

Rim Sghiri  1 , Hana Benhassine  2 , Khadija Baccouche  3 , Meriem Ghozzi  2 , Sarra Jriri  3 , Zahid Shakoor  4 , Adel Almogren  4 , Foued Slama  2 , Nadia Idriss  2 , Zeineb Benlamine  2 , Elyes Bouajina  3 , Ramzi Zemni  2
Affiliations

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

Rim Sghiri et al. Clin Rheumatol. 2022 Jun.

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.

Keywords: Bone mineral density; CD40; IFIH1; IRAK-1; IRAK-2; Osteopenia; Osteoporosis; Rheumatoid arthritis; TNFAIP3; miR146-a.

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