IL-17A, IL-17F and IL-23R Gene Polymorphisms in Polish Patients with Rheumatoid Arthritis.
Among the complex network of inflammatory cells involved in the pathogenesis of rheumatoid arthritis (RA), Th17 cells have recently been identified as key cells in the promotion of autoimmune processes, and joint destruction. The IL-23/Th17 signalling pathway, consisting of IL-23/IL-23R, IL-17A and IL-17F encoding genes, represents a candidate way for RA development with possible involvement in disease susceptibility and effect on disease progression. The present study aimed to determine the association between the polymorphic variants of the IL-17A (rs2275913), IL-17F (rs763780) and IL-23R (rs11209026) genes and RA susceptibility, progression and response to therapy with TNF-α inhibitors. Eighty-nine patients and 125 healthy individuals were investigated. The IL-17A polymorphism was found to affect RA progression and response to anti-TNF treatment. Female patients carrying the IL-17A wild-type genotype more frequently presented with stage 4 (8/24 vs. 6/47; p = 0.058) and were characterized by more active disease (the highest DAS28 score >5.1) after 3 months of therapy with the TNF inhibitors (12/23 vs. 15/45; p = 0.040). The IL-17F polymorphism appeared to be associated with susceptibility to the disease. The presence of the IL-17F minor variant (OR 3.97; p < 0.001) and its homozygosity (OR 29.62; p < 0.001) was more frequent among patients than healthy individuals. These results suggest that the polymorphisms within the IL-17A and IL-17F genes play a significant role in RA.
Laboratory of Clinical Immunogenetics and Pharmacogenetics, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland, bogunia@iitd.pan.wroc.pl.
Katarzyna
K
Bogunia-Kubik
Jerzy
J
Świerkot
Anna
A
Malak
Barbara
B
Wysoczańska
Beata
B
Nowak
Katarzyna
K
Białowąs
Katarzyna
K
Gębura
Lucyna
L
Korman
Piotr
P
Wiland
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D018450:Disease Progression; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D012737:Sex Factors; D058504:Th17 Cells / Q000502:physiology*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
D018501:Antirheumatic Agents; C515500:IL23R protein, human; D020381:Interleukin-17; D018123:Receptors, Interleukin; D014409:Tumor Necrosis Factor-alpha