Genetic variations in the IL-12B gene in association with IL-23 and IL-12p40 serum levels in ankylosing spondylitis
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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.
KeywordsAnkylosing spondylitis Genetic predisposition to disease Cytokines
Research concept and design: Mariana Ivanova, Irena Manolova, Spaska Stanilova. Data collection: Mariana Ivanova, Irena Manolova, Lyuba Miteva, Rada Gancheva. Data analysis and interpretation: Irena Manolova, Mariana Ivanova, Lyuba Miteva, Rada Gancheva, Rumen Stoilov, Spaska Stanilova. Writing the article: Mariana Ivanova, Irena Manolova, Critical revision of the article: Spaska Stanilova, Rumen Stoilov.
This work was supported by the Fund for Scientific and Mobile Project of the Faculty of Medicine, Trakia University, Stara Zagora, Bulgaria; Grant No. 2/2016.
Compliance with ethical standards
Conflict of interest
The authors declare that there is no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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