title: Association of IL17A and IL17F genes with rheumatoid arthritis disease and the impact of genetic polymorphisms on response to treatment.
abstract: Previous studies have reported an association between polymorphisms in Il17A and IL17F genes and the prevalence of rheumatoid arthritis (RA) in Caucasian populations. The aim of the current study was to investigate that polymorphisms in both genes may affect RA susceptibility in the Tunisian population and to study the relation between serum IL-17 levels and synovial fluid (SF) levels and risk in RA patients. We suggested also that these polymorphisms may influence response to treatment in Tunisian RA patients.
  
  
  
  We studied IL17A-152 G/A (rs2275913), IL17F 7488 A/G (rs763780) and IL17F 7383 A/G polymorphisms in a Tunisian population. The genotypic and allelic distributions of IL-17A and IL-17F genes polymorphisms were analyzed by Polymerase Chain-Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) for 108 patients and 202 healthy controls. IL-17 levels were measured in synovial fluid (SF) and in serum of both 108 patients and 47 controls (pg/ml) using enzyme-linked immunosorbent assay (ELISA) technique.
  
  
  
  Our results indicated that IL17F 7488 A/G and IL17F 7383 A/G polymorphisms were significantly associated with RA risk in the whole population. However, IL17A-152 G/A polymorphism did not show any significant association with RA prevalence in the Tunisian population. Stratification according to demographic and clinical features revealed differential significant associations of IL17A-152 G/A, IL17F 7488 A/G and IL17F 7383 A/G polymorphisms within different subgroups and subtypes of clinical-pathologic features in RA patients. IL17A-152 G/A polymorphism was associated with an enhanced response to biologic and MTX treatment. IL17F 7383 A/G polymorphism was associated with an enhanced response to biologic treatment. The IL17F 7488 A/G polymorphism decreased significantly good response to biologic treatment, but enhanced response to MTX treatment. The expression of IL-17 in serum and synovial fluid (SF) in RA patients was significantly higher than that observed in healthy controls (P<0.0001) and their levels depend on RA severity. The mean IL-17 levels in the anti-TNF α treated patients decreased significantly at 0 week, 14 weeks and 30 weeks (P=0.0032 and P<0.0001, respectively).
  
  
  
  Our results confirmed IL17A and IL17F as potential candidate genes involved in RA. They play pivoting roles in the susceptibility and in clinical features of RA disease. Responses to RA treatments are differently conditioned by polymorphisms in IL17A and IL17F genes.
authors.affiliation: Unit Research 12SP15 "Homeostasis and Cell Dysfunction", Abderrahman Mami Hospital, Ariana, Tunisie; University of Tunis El Manar, Faculty of Medicine of Tunis, Department of Basic Sciences, Tunis, Tunisie. Electronic address: marwa_ouled_salah@hotmail.fr.
authors.forename: Ouled Salah
authors.initials: OS
authors.lastname: Marwa
authors.affiliation: Unit Research 12SP15 "Homeostasis and Cell Dysfunction", Abderrahman Mami Hospital, Ariana, Tunisie; University of Tunis El Manar, Faculty of Medicine of Tunis, Department of Basic Sciences, Tunis, Tunisie.
authors.forename: Tizaoui
authors.initials: T
authors.lastname: Kalthoum
authors.affiliation: Unit Research 12SP15 "Homeostasis and Cell Dysfunction", Abderrahman Mami Hospital, Ariana, Tunisie; University of Tunis El Manar, Faculty of Medicine of Tunis, Department of Basic Sciences, Tunis, Tunisie.
authors.forename: Kaabachi
authors.initials: K
authors.lastname: Wajih
authors.affiliation: Unit Research 12SP15 "Homeostasis and Cell Dysfunction", Abderrahman Mami Hospital, Ariana, Tunisie.
authors.forename: Hamzaoui
authors.initials: H
authors.lastname: Kamel
mesh_terms: D000328:Adult; D000483:Alleles; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D015415:Biomarkers; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012307:Risk Factors; D012720:Severity of Illness Index; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; C508717:IL17A protein, human; C440021:IL17F protein, human; D020381:Interleukin-17; D008727:Methotrexate
keywords: IL17A gene; IL17F gene; Polymorphism; Rheumatoid arthritis; Treatment