Impact of IL12B Polymorphisms on Genetic Susceptibility and IL-12p40 and IL-23 Serum Levels in Rheumatoid Arthritis.

Publisher: Informa Healthcare Country of Publication: England NLM ID: 8504629 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-4311 (Electronic) Linking ISSN: 08820139 NLM ISO Abbreviation: Immunol Invest Subsets: MEDLINE

Publication: London : Informa Healthcare
Original Publication: New York, N.Y. : M. Dekker, c1985-

Arthritis, Rheumatoid/*genetics ; Genetic Predisposition to Disease/*genetics ; Interleukin-12 Subunit p40/*blood ; Interleukin-23/*blood; Adolescent ; Adult ; Aged ; Arthritis, Rheumatoid/blood ; Arthritis, Rheumatoid/immunology ; Bulgaria ; Cross-Sectional Studies ; Female ; Genotype ; Humans ; Interleukin-12 Subunit p40/genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Young Adult

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.

Keywords: IL12B haplotypes; RA; Rs17860508; SNP; rs3212227

0 (IL12B protein, human)
0 (Interleukin-12 Subunit p40)
0 (Interleukin-23)

Date Created: 20190605 Date Completed: 20200604 Latest Revision: 20200604

20250114

10.1080/08820139.2019.1622561

31161840