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Abstract Number: 92

Variation at Interleukin-6 Receptor Gene Is Associated to Joint Damage in Rheumatoid Arthritis

María López-Lasanta1, Antonio Julià1, Joan Maymo2, Benjamin Fernandez Gutierrez3, Inmaculada Ureña4, Francisco J. Blanco5, Juan D. Cañete6, Mercedes Alperi-López7, Alejandro Olivé8, Hector Corominas9, Jesús Tornero10, Alba Erra11, Miriam Almirall12, Nuria Palau13, Ana M. Ortiz Garcia14, Gabriela Avila13, Luis Rodriguez-Rodriguez15, Arnald Alonso1, Raül Tortosa1, Isidoro González-Alvaro16 and Sara Marsal1, 1Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, Barcelona, Spain, 2Rheumatology, Hospital del Mar, Barcelona, Spain, 3Department of Rheumatology, Hospital Clínico San Carlos, Madrid, Spain, 4Rheumatology service, Hospital Regional Universitario Carlos Haya, Malaga, Spain, 5Osteoarticular and Aging Research Lab, INIBIC–Complejo Hospitalario Universitario A Coruña, A Coruña, Spain, 6Arthritis Unit. Rheumatology, Arthritis Unit. Rheumatology Department. Hospital Clínic, Barcelona, Spain, 7Department of Rheumatology, Hospital Universitario Central de Asturias, Asturias, Spain, 8Rheumatology, Hospital Germans Trias i Pujol, Badalona, Spain, 9Rheumatology, Hospital de Sant Joan Despí Moisès Broggi, Barcelona, Spain, 10Rheumatology Department, Hospital Universitario Guadalajara, Guadalajara, Spain, 11Rheumatology, Rheumatology Hospital San Rafael, Barcelona, Spain, 12Rheumatology Department, Hospital del Mar, Barcelona, Spain, 13Vall d'Hebron Hospital Research Institute, Barcelona, Spain, 14Rheumatology, H.U. La Princesa, Madrid, Spain, 15Department of Rheumatology, Hospital Clinico San Carlos, Madrid, Spain, 16Rheumatology, Hospital Universitario de La Princesa. IIS La Princesa, Madrid, Spain

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Biomarkers, IL-6R signaling, joint damage and rheumatoid arthritis (RA)

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Session Information

Date: Sunday, November 8, 2015

Session Title: Genetics, Genomics and Proteomics Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Interleukin-6 (IL-6) cytokine signaling is key
in Rheumatoid Arthritis (RA) pathophysiology. Blocking IL-6 receptor
(IL6R) has proven to be a highly effective treatment to prevent joint damage.
This study was performed to investigate the association between the genetic
variation atIL6R gene and the severity of joint damage in RA.

Methods: IL6R gene
tagging SNPs (n=5, Figure 1) were genotyped in a discovery group of 527 RA
patients from 5 different university hospitals from Spain. For each marker, a multivariate
linear regression analysis was performed to test for association with joint
damage and also to  adjust several covariates including years disease evolution,
autoantibody status and gender. Haplotypes combining the SNPs were also
estimated and tested for association with the level of joint destruction. Using
an independent cohort of 705 RA patients from 6 university hospitals we
performed a validation study of the SNPs associated in the discovery phase.

Results: In the discovery group we found a highly significant
association between IL6R SNP rs4845618 and the level of joint
destruction in RA (P=0.0058, Table 1), and a moderate association with
SNP rs4453032 (P=0.02, Table 1). The resulting haplotype from both SNPs
was more significantly associated with joint damage (P=0.0037). Using
the validation cohort, we replicated the association between the two IL-6R SNPs
with the degree of joint destruction in RA (P=0.007 and P=0.04,
meta-analysis P=0.00011 and P=0.0021, respectively,
Table 1), and the haplotype association ( P=0.0058,
meta-analysis P=6.64 e-5).

Figure 1. LD pattern at IL6R locus. The two main haplotype blocks covering most common genetic variation
at IL6R gene (in blue) are indicated by solid line triangles.

Table 1. Association of IL6R markers
with the severity of joint damage in RA.
Significance
values for IL6R SNPs in the discovery, replication cohorts as well
meta-analysis of the two cohorts.

SNP

Basepair

MAF

P-Discovery

P-Replication

Meta-analysis P

rs4845618

154400015

0.44

0.0052

0.007

0.00011

rs4453032

154414086

0.4

0.51

–

–

rs4845374

154426947

0.17

0.02

0.04

0.0021

rs6698040

154432948

0.21

0.11

–

–

rs4379670

154439865

0.16

0.25

–

–

Conclusion:  We show for the first time that genetic variation
at IL6R gene is associated to joint damage in RA.

 


Disclosure: M. López-Lasanta, None; A. Julià, None; J. Maymo, None; B. Fernandez Gutierrez, None; I. Ureña, None; F. J. Blanco, Pfizer, Bioiberica, and Gebro Pharma, 5; J. D. Cañete, None; M. Alperi-López, None; A. Olivé, None; H. Corominas, None; J. Tornero, None; A. Erra, None; M. Almirall, None; N. Palau, None; A. M. Ortiz Garcia, Spanish Society of Rheumatology, 2; G. Avila, None; L. Rodriguez-Rodriguez, None; A. Alonso, None; R. Tortosa, None; I. González-Alvaro, None; S. Marsal, None.

To cite this abstract in AMA style:

López-Lasanta M, Julià A, Maymo J, Fernandez Gutierrez B, Ureña I, Blanco FJ, Cañete JD, Alperi-López M, Olivé A, Corominas H, Tornero J, Erra A, Almirall M, Palau N, Ortiz Garcia AM, Avila G, Rodriguez-Rodriguez L, Alonso A, Tortosa R, González-Alvaro I, Marsal S. Variation at Interleukin-6 Receptor Gene Is Associated to Joint Damage in Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/variation-at-interleukin-6-receptor-gene-is-associated-to-joint-damage-in-rheumatoid-arthritis/. Accessed February 27, 2021.
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