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.
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.
Authors: A Martínez; J Varadé; J R Lamas; M Fernández-Arquero; J A Jover; E G de la Concha; B Fernández-Gutiérrez; E Urcelay Journal: Ann Rheum Dis Date: 2008-01 Impact factor: 19.103
Authors: Upneet K Sokhi; Mark P Liber; Laura Frye; Sungho Park; Kyuho Kang; Tania Pannellini; Baohong Zhao; Rada Norinsky; Lionel B Ivashkiv; Shiaoching Gong Journal: Nat Commun Date: 2018-02-13 Impact factor: 14.919
Authors: Harm-Jan Westra; Marta Martínez-Bonet; Suna Onengut-Gumuscu; Annette Lee; Yang Luo; Nikola Teslovich; Jane Worthington; Javier Martin; Tom Huizinga; Lars Klareskog; Solbritt Rantapaa-Dahlqvist; Wei-Min Chen; Aaron Quinlan; John A Todd; Steve Eyre; Peter A Nigrovic; Peter K Gregersen; Stephen S Rich; Soumya Raychaudhuri Journal: Nat Genet Date: 2018-09-17 Impact factor: 41.307