In:
Journal of Clinical Microbiology, American Society for Microbiology, Vol. 56, No. 4 ( 2018-04)
Abstract:
Naturally occurring functional variants (rs148314165 and rs200820567, collectively referred to as TT 〉 A) reduce the expression of the tumor necrosis factor alpha-induced protein 3 ( TNFAIP3 ) gene, a negative regulator of NF-κB signaling, and predispose individuals to autoimmune disease. In this analysis, we conducted a genetic association study of the TT 〉 A variants in 1,209 controls and 150 patients with brucellosis, an infectious disease, and further assessed the role of the variants in brucellosis. Our data demonstrated that the TT 〉 A variants were correlated with cases of brucellosis ( P = 0.002; odds ratio [OR] = 0.34) and with individuals who had a positive serum agglutination test (SAT) result (titer of 〉 1/160) ( P = 4.2 × 10 −6 ; OR = 0.23). A functional study demonstrated that brucellosis patients carrying the protective allele (A) showed significantly lower expression levels of the TNFAIP3 gene in their peripheral blood mononuclear cells and showed increased NF-κB signaling. Monocytes from individuals carrying the A allele that were stimulated with Brucella abortus had lower mRNA levels of TNFAIP3 and produced more interleukin-10 (IL-10), IL-6, and IL-1β than those from TT allele carriers. These data showed that autoimmune disease-associated risk variants, TT 〉 A, of the TNFAIP3 locus play a protective role in the pathogenesis of brucellosis. Our findings suggest that a disruption of the normal function of the TNFAIP3 gene might serve as a therapeutic target for the treatment of brucellosis.
Type of Medium:
Online Resource
ISSN:
0095-1137
,
1098-660X
DOI:
10.1128/JCM.01363-17
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2018
detail.hit.zdb_id:
1498353-9
SSG:
12
Bookmarklink