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 ankylosing spondylitis (AS). Although the precise etiology of AS is unclear, high prevalence of HLA-B27 predisposition and predominantly involved pro-inflammatory cytokines suggest a substantial association with an immunogenetic basis and support the hypothesis that IL12B gene polymorphisms could affect the development of AS.
Objectives In this regard, the aimof this study was to determine whether genetic polymorphisms of the IL-12B gene are associated with AS in Bulgarian populationby genotyping for A/C SNP in the 3′-UTR of the IL-12B (rs3212227) and 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 58 patients with AS and 132 matched healthy individuals were enrolled it the study. Genotyping for the rs3212227was performed by restriction fragment length polymorphisms-PCR assay and for the rs17860508 by allele specific-PCR.
Results There were no significant differences in the genotype and allele frequencies of rs3212227 and rs17860508 polymorphism of the IL12B between AS patients and controls. However, in logistic regression analysis the presence of 3′-UTR allele C in the genotype (CT + CC vs. TT) and IL12Bpro allele 2 in the genotype (1.2+2.2 vs. 1.1) were associated with an increasing risk of developing AS (OR=1.454 and OR-2.04, respectively). Also, AS patients carrying 3′-UTR CC genotype had earlier age at diseases onset (20.6±5.97 years) than those carrying allele A in the genotype (AA+AC; 27.8±7.93 years; p=0.054). In addition, the presence of IL12Bpro allele 2 in the genotype (1.2+2.2 vs. 1.1) is associated with increased risk of peripheral joints involvement (OR=2.625) and the carriage of IL12Bpro genotype 2.2 is associated with 2-fold increased risk of having higher functional disability (BASFI>4; OR=2.286).
Conclusions In conclusion, our data support the hypothesis that genetic variations in IL12B gene affecting inducible production of IL-12p40, may contribute to development of AS in the Bulgarian population.
Disclosure of Interest None Declared