Genetic variations in the IL-12B gene in association with IL-23 and IL-12p40 serum levels in ankylosing spondylitis

In the present study, we evaluated the implication of IL12Bpro (rs17860508) and IL12B 3′ UTR A/C single nucleotide polymorphisms (SNPs) (rs3212227) for the ankylosing spondylitis (AS) development and the impact of IL12B genetic variations on IL-23 and IL-12p40 production and musculoskeletal disease characteristics. 80 patients with AS and 242 healthy controls were studied. Genotyping for the rs3212227 was performed by restriction fragment length polymorphisms–polymerase chain reaction (PCR) and for the rs17860508 by allele-specific PCR. Cytokines were measured by an enzyme-linked immunosorbent assay (ELISA). Clinical status was evaluated by calculation of the Ankylosing Spondylitis Disease Activity Score (ASDAS) using the C-reactive protein (CRP) level, the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Metrology Index (BASMI). An association was found for the rs17860508 polymorphism with AS under the allelic, the dominant, and the co-dominant models. Rs3212227 was not attributable to AS susceptibility by itself, but the carriage of C allele in the genotype amplifies the genetic risk for AS in the carriers of the high-risk IL12Bpro 2-allele, especially in homozygosity. Circulating IL-23 and IL-12p40 were raised among AS patients, as some of the genotypes of both IL12B polymorphisms positively regulate their expression. Carriage of the IL12Bpro genotype 2.2 has been linked to a worsened functional disability, while 3′ UTR CC genotype—with severe disease activity. IL12B polymorphisms can impact AS susceptibility and modulate IL-23 and IL-12p40 production levels, and have a contribution to the disease phenotype.