title: Levels of interleukin-(IL)-12p40 are markedly increased in Brucellosis among patients with specific IL-12B genotypes.
abstract: Brucellosis remains a major zoonosis worldwide. Brucella antigens induce the production of T-helper 1 (Th1) cytokines such as interleukin-12 (IL-12) in humans. We aimed to investigate the association of two single nucleotide polymorphisms (SNPs) in the gene encoding the IL-12p40 cytokine (IL-12B) with brucellosis and to examine the functionality of these SNPs through measuring serum levels of IL-12p40. We genotyped IL-12B gene rs3212227, A>C; rs6887695 G>C polymorphisms in a case-control study on a total of 281 subjects including 153 patients with active brucellosis and 128 healthy controls, using RFLP and serum IL-12p40 levels, were assessed by ELISA. The rs3212227 minor allele (C) and homozygote genotype (CC) were more frequent in controls compared with patients with brucellosis (P = 0.006, OR = 0.608, 95%CI = 0.429-0.861 for the C allele; P = 0.024, OR = 0.443, 95% CI: 0.218-0.900 for the CC genotype). Comparison of IL-12B genotypes and serum levels of the IL-12p40 revealed that rs3212227 AA genotype, with higher frequency in patients than in controls, was associated with increased levels of the cytokine (P = 0.0001). Furthermore, the distribution of haplotype and genotype combinations in our study suggested that rs3212227C/rs6887695C haplotype or CC/GC or CC/CC genotype combinations may protect controls against Brucella infection by contributing to a functional downregulation of the serum IL-12p40 production in vivo, as shown by ELISA (P < 0.05). Overall, our study demonstrated that rs3212227 A variant was associated with higher levels of serum IL-12p40 and could possibly contribute to an inherited predisposition to brucellosis.
authors.affiliation: Infectious Diseases and Tropical Medicine Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.
authors.forename: E
authors.initials: E
authors.lastname: Eskandari-Nasab
authors.forename: M
authors.initials: M
authors.lastname: Moghadampour
authors.forename: A
authors.initials: A
authors.lastname: Asadi-Saghandi
authors.forename: E
authors.initials: E
authors.lastname: Kharazi-Nejad
authors.forename: A
authors.initials: A
authors.lastname: Rezaeifar
authors.forename: H
authors.initials: H
authors.lastname: Pourmasoumi
mesh_terms: D000328:Adult; D002006:Brucellosis / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000097:blood* / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C500879:IL12B protein, human; D053762:Interleukin-12 Subunit p40