Association of Polymorphisms on OPG, RANK and RANKL with ACPA Presence and Erosions: Results of a Meta-Analysis on 1570 Rheumatoid Arthritis Patients from 3 French Cohorts

Adeline Ruyssen Witrand^1,2,3, Sara Scaramuzzino^1,2, Delphine Nigon⁴, Cédric Lukas⁵, Yannick Allanore⁶, Olivier Vittecoq⁷, Thierry Schaeverbeke⁸, Jacques Morel⁹, Jean Sibilia¹⁰, Anne Cambon-Thomsen^1,2, Alain G. Cantagrel¹¹, Philippe Dieude^12,13 and Arnaud Constantin⁴, ¹UMR 1027, Inserm, Toulouse, France, ²UMR 1027, University Paul Sabatier, Toulouse, France, ³Rheumatolgy, CHU Purpan - Hôpital Pierre-Paul Riquet, Toulouse, France, ⁴Rheumatology, CHU Purpan - Hôpital Pierre-Paul Riquet, Toulouse, France, ⁵Immuno-Rhumatologie, Hopital Lapeyronie, Montpellier, France, ⁶Department of Rheumatology, University Paris Descartes and Cochin Hospital, Paris, France, ⁷Rheumatology, Department of Rheumatology, Rouen University Hospital & Inserm 905, Institute for Biomedical Research, University of Rouen, Rouen, France, ⁸Rheumatology, Bordeaux University Hospital, Bordeaux, France, ⁹Department of Rheumatology, Hôpital Lapeyronie, Montpellier, France, ¹⁰Division of Rheumatology, University Hospital of Strasbourg, Strasbourg, France, ¹¹Centre Hospitalier Universitaire de Toulouse, Toulouse, France, ¹²Rheumatology, Rheumatology departement & INSERM U699, Paris Diderot university, APHP, Bichat hospital, Paris, France, ¹³Rhumatologie, Hopital Bichat Claude Bernard, Paris, France

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: ACPA, polymorphism, rheumatoid arthritis (RA) and severity

Session Information

Title: Genetics, Genomics and Proteomics II

Session Type: Abstract Submissions (ACR)

Background/Purpose

Rheumatoid Arthritis (RA) is a multifactorial complex disease characterized by the presence of anti-citrullinated peptides antibodies (ACPA) and joints erosions. The mechanisms of bone erosions in RA are mediated by the RANK-RANKL-Osteoprotegerin (OPG) system. Some single nucleotide polymorphisms (SNPs) on RANK, RANKL and OPG genes have been previously associated with RA susceptibility. The aim of this study was to assess the association between 1 SNP on RANK (rs8086340), 3 SNPs on RANKL (rs7984870, rs7325635, rs1054016) and 1 SNP on OPG(rs2073618) and ACPA presence or joint erosions.

Methods

Patients: the study was based on 3 French cohorts: ESPOIR cohort (n=632 early RA patients, 76% of females, mean age: 50 years, ACPA+: 49%, presence of erosions in 36,6%), RMP cohort (n=249 early RA patients, 75% of females, mean age: 50 years, ACPA+: 73%, presence of erosions in 39%) and FRAGC-PRI cohort (n=689 long-standing RA patients, 76% of females, mean age: 61 years, ACPA+: 62%, presence of erosions in 68%). Genotyping: the 5 SNPs located on RANK, RANKL and OPG were genotyped by Kbiosciences (GB). Statistical analysis: The proportion of patients with ACPA presence or presence of erosions were compared according to the allele carriage of each SNP by a Chi square test for each cohort separately. A meta-analysis on the 3 cohorts assessing the risk of ACPA presence or the risk of erosions according to the allele carriage of each SNP was performed using Mantel-Haenszel method. Results were expressed as Odds ratios (OR) and 95% confidence intervals (95%CI). Correction for multiple tests was performed using Bonferroni method (significance set at p=0.005)

Results

After meta-analysis performed on the 3 cohorts, 1 SNP located on RANKL had a protective effect against ACPA presence after Bonferroni correction: G allele of rs7325635 carriage: OR=0.63 [0.47-0.86], p=0.003, whereas the 2 other SNPs were not significantly associated with ACPA presence when Bonferroni correction was applied (G allele of rs1054016 carriage: OR=0.67 [95%CI: 0.49-0.91], p=0.01, , G allele carriage of rs7984870: OR=0.71 [0.54-0.93], p=0.01). Furthermore, the SNP located on RANK had also a protective effect on ACPA presence: C allele of rs8086340: OR=0.64 [0.50-0.81], p=0,0003. However, these SNPs were not significantly associated with the risk of erosions. The SNP located on OPG was significantly associated with a protection against erosions after Bonferroni correction: G allele carriage of rs2073618: OR=0.68 [0.52-0.88], p=0.004.

Conclusion

This meta-analysis performed on 3 French cohorts identified 1 SNP located on RANKL, 1 SNP located on RANK associated with protection against ACPA presence and 1 SNP located on OPG associated with protection against erosions in RA.

Disclosure:

A. Ruyssen Witrand,
None;

S. Scaramuzzino,
None;

D. Nigon,
None;

C. Lukas,
None;

Y. Allanore,
None;

O. Vittecoq,
None;

T. Schaeverbeke,
None;

J. Morel,
None;

J. Sibilia,
None;

A. Cambon-Thomsen,
None;

A. G. Cantagrel,
None;

P. Dieude,
None;

A. Constantin,
None.

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