Variation at interleukin-6 receptor gene is associated to joint damage in rheumatoid arthritis

Arthritis Research & Therapy
Maria Lopez-LasantaSara Marsal

Abstract

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 at IL6R gene and the severity of joint damage in RA. IL6R gene tagging SNPs (n = 5) were genotyped in a discovery group of 527 RA patients from 5 different university hospitals from Spain. For each marker, a linear regression analysis was performed using an additive model and adjusting for the years of evolution of the disease, autoantibody status, gender and age. 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. 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, P corrected = 0.026), and a moderate association with SNP rs4453032 (P = 0.02, P corrected = 0.05). The resulting haplotype from both SNPs was more significantly associated with joint da...Continue Reading

References

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Citations

Dec 14, 2016·The Pharmacogenomics Journal·M Maldonado-MontoroM Ángel Calleja-Hernández
Aug 14, 2019·Biomolecules·Agnieszka Paradowska-GoryckaMarzena Olesinska
Apr 25, 2018·Frontiers in Immunology·Irene Maeve ReaOwen A Ross
Apr 16, 2020·International Journal of Inflammation·Marek CieślaDorota Darmochwał-Kolarz
Jul 16, 2020·International Journal of Molecular Sciences·Dmitry S MikhaylenkoAndrey A Zamyatnin
Jul 2, 2021·Molecular Biology Reports·Muhammad Zhaid HussainAhmed Ammar Cheema

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Methods Mentioned

BETA
genotyping
PCR

Software Mentioned

R
Haploview
Hapmap
PLINK
METAL

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