Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.


Association of rs8192284 IL-6 Receptor Polymorphism and Soluble IL-6 Receptor Plasma Concentration with Disease Activity in Rheumatoid Arthritis

Rodriguez-Rodriguez1,  L., Lamas1,  José Ramón, Gonzalez-Vigo2,  A., Lopez-Romero3,  P., Tornero-Esteban1,  P., Abasolo1,  L., Varade2,  J.

Hospital Clínico San Carlos, Madrid, Spain
Immunology Service, Hospital Clinico San Carlos, Madrid, Spain
CNIC, Madrid, Spain
Immunology Service, Hospital Clínico San Carlos, Madrid, Spain
Hospital Clinico San Carlos, Madrid, Spain

Purpose:

Interleukin 6 soluble receptor a subunit (sIL-6R) is mainly generated by shedding of the membrane-bound form. This process is influenced by the single nucleotide polymorphism rs8192284 (A>C) resulting in an Aspartic acid to Alanine substitution (D358A) located at the proteolitic cleavage site. The aim of this paper is to characterize whether plasma levels of sIL6R may be influenced by rs8192284 in Rheumatoid Arthritis patients and to address the association of sIL-6R plasma levels and SNP with disease activity.

Method:

39 patients were randomly selected from a cohort of RA patients of Spaniard descent. Plasma sIL-6R concentration was measured using an ELISA sandwich. Genotyping of rs8192284 (A>C) polymorphism was done using a Fast Real-Time PCR System. DAS 28 score was used to assess disease activity. Data are indicated as mean (standard deviation).

Results:

sIL-6R plasma levels are positively associated to the number of C alleles (AA: 35.27 (3.50) ng/ml, AC: 45.50 (4.58) ng/ml, CC: 52.55 (3.18) ng/ml, p<0.0001). DAS28 and sIL-6R plasma levels showed a positive association in the anti-CCP positive subgroup (r2=0.4257, p=0.0482) and a negative association in the anti-CCP negative subgroup (r2=-0.5466, p=0.0284). Also an association between DAS28 and SNP was showed: C allele carrier was positively related to DAS28 in the anti-CCP positive subgroup (4.68 (1.11) vs. 3.57 (1.12), p=0.0310) and it was negatively associated in the anti-CCP negative subgroup (3.36 (1.03) vs. 6.37 (1.10), p=0.0002).

Conclusion:

Our findings showed that rs8192284 polymorphism is operative in RA patients. The presence of anti-CCP antibodies determines the relationship between sIL-6R concentration, genotype and disease activity. RA anti-CCP positive patients carrying the C allele of rs8192284 SNP would be the ideal target for IL-6R blocking agents.

To cite this abstract, please use the following information:
Rodriguez-Rodriguez, L., Lamas, José Ramón, Gonzalez-Vigo, A., Lopez-Romero, P., Tornero-Esteban, P., Abasolo, L., et al; Association of rs8192284 IL-6 Receptor Polymorphism and Soluble IL-6 Receptor Plasma Concentration with Disease Activity in Rheumatoid Arthritis [abstract]. Arthritis Rheum 2009;60 Suppl 10 :384
DOI: 10.1002/art.25467

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