AB0076 Promoter IL12B Gene Polymorphism Contributes to Rheumatoid Arthritis Development. (10th June 2014)

• Record Type: Journal Article
• Authors: Ivanova Goycheva, M.; Stoilov, R.; Rashkov, R.; Stanilova, S.; Manolova, I.
• Is Part Of: Annals of the rheumatic diseases. Volume 73:Supplement 2(2014)
• Page Start: 829
• Page End: 829
• Publication Date: 2014-06-10
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2014-eular.2716
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: IL12B encodes the IL-12p40 subunit of both the IL-12 and IL-23 cytokines, which play critical and unique roles in bridging the innate and adaptive immune systems. Whereas IL-12 induces development of Th1 cells, which produce IFN-gamma, IL-23 is involved in Th-17 cells that appear to play a role in the pathogenesis of rheumatoid arthritis (RA). Although the precise RA etiology is not fully understood, a strong genetic component has been established. The best-characterized genetic factor contributing to RA is the association of different HLA-DRB1 alleles with the disease. However, other non-HLA genes also play a relevant role in RA and it is proposed that IL12B gene polymorphisms could affect the development of RA. Objectives: In this regard, the aim of this study was to determine whether genetic polymorphisms of the IL-12B gene are associated with RA in Bulgarian population by genotyping for IL12Bpro (rs17860508), a complex polymorphism in promoter region of the IL12B, resulting from 4 bp microinsertion combined with AA/GC transition. Methods: A total of 136 patients with RA and 125 matched healthy individuals were enrolled it the study. Genotyping for the rs17860508 was performed by allele specific-PCR. Results: In logistic regression analysis the presence of IL12Bpro allele 2 in the genotype (1.2+2.2 vs. 1.1) was associated with an increased risk of developing RA (OR=1.44) and the presence of IL12Bpro allele 1 in the genotype (1.2+1.1 vs. 2.2) was associated with a decreased risk of developing RA (OR=0.68). However, there were no significant differences in the genotype and allele frequencies of rs17860508 polymorphism of the IL12B between RA patients and controls. The presence of IL12Bpro allele 1 in the genotype (1.2+1.1 vs. 2.2) was associated with decreased risk of early disease onset (age at onset<48; OR=0.48) and the carriage of IL12Bpro genotype 1.1 was associated with 2-fold decreased risk of having higher disease severity (DAS28>5.1; OR=0.571). These results suppose that IL12Bpro 1.1 genotype could be protective, whether 2.2 genotype might be predisposing to susceptibility of RA. Conclusions: In conclusion, our data support the hypothesis that genetic variations in IL12B gene affecting inducible production of IL-12p40, contribute to the development of RA in the Bulgarian population. Disclosure of Interest: None declared DOI: 10.1136/annrheumdis-2014-eular.2716