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