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  • Title: Impact of IL12B Polymorphisms on Genetic Susceptibility and IL-12p40 and IL-23 Serum Levels in Rheumatoid Arthritis.
    Author: Manolova I, Ivanova M, Vasilev G, Stoilov R, Miteva L, Stanilova S.
    Journal: Immunol Invest; 2020 Feb; 49(1-2):1-14. PubMed ID: 31161840.
    Abstract:
    The aim of this study was to evaluate the possible association of IL12B gene polymorphisms with serum levels of IL-12p40, IL-23 and genetic susceptibility to rheumatoid arthritis (RA) in the Bulgarian population. Genotyping for IL12Bpro (rs17860508) and IL12B A/C - 3' UTR (rs3212227) polymorphisms was performed by polymerase chain reaction (PCR)-based methods in 125 RA patients and 239 healthy controls. The IL-23 and IL-12p40 serum levels were measured by enzyme-linked immunosorbent assay (ELISA). An association was established between the rs17860508 polymorphism and RA susceptibility in Bulgarian population with an increased frequency of rs17860508 minor allele-2 and homozygous genotype-22 in RA patients. The rs17860508 risk RA genotype-22 was also significantly correlated to elevated serum IL-23 in RA patients. Although, there was no association between the rs3212227 and genetic predisposition to RA, significantly increased serum levels of both Il-12p40 and IL-23 were observed in RA patients with the rs3212227 AA genotype. Furthermore, the distribution of haplotypes and genotype combination in our cohort indicated increased RA risk in individuals carrying the rs17860508/rs3212227 2/A haplotype or 2.2/AC+CC combination, while 1/A haplotype or 1.1/AA combination may be protective for RA. In conclusion, our study demonstrates a functional effect of IL12B polymorphisms on IL-12p40 and IL-23 cytokine levels in RA patients and suggests a leading role for IL12B rs17860508 in the genetic predisposition to RA, while IL12B rs3212227 significantly modify the RA risk in Bulgarian population.
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