Association of TBX21 promoter polymorphisms with type 1 autoimmune hepatitis in a Chinese population

• Published in: Human immunology 2011, Vol.72 (1), p.69-73
• Main Authors: Chen, Song, Zhao, Wenli, Tan, Wenting, Luo, Xiao, Dan, Yunjie, You, Zhonglan, Kuang, Xuemei, Wang, Yuming, Deng, Guohong
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Allergy and Immunology; Autoimmune hepatitis; CD4-Positive T-Lymphocytes; China; Female; Genetic Predisposition to Disease; Genotype; Hepatitis, Autoimmune - genetics; Humans; Male; Middle Aged; Polymorphism, Genetic; Promoter Regions, Genetic; Single nucleotide polymorphism; Survival Analysis; T-Box Domain Proteins - genetics; TBX21 T-bet; Th1 Cells; Young Adult
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2010.10.019

Abstract The T-box transcription factor T-bet is a key regulator for the lineage commitment in CD4 Th1 cells and CD8 T cells by activating the hallmark production of interferon-γ, and its expression level is linked to autoimmune diseases. T-1993C and T-1514C polymorphisms in the TBX21 gene (encoding T-bet) promoter can affect transcription activity. We investigated the distributions of these functional polymorphisms in 84 adult patients with type 1 autoimmune hepatitis (AIH-1) and 318 healthy controls. Intracellular T-bet staining of polarized CD4 Th1 cells from healthy controls corresponding to T-1993C genotypes were analyzed by flow cytometry. The −1993C allele frequency was 3.0% in AIH-1 and 11.8% in controls ( p = 0.000 25). Individuals carrying the −1993C allele had a decreased risk to AIH-1 compared with those without the −1993C allele ( p = 0.0016, odds ratio [OR] = 0.22, 95% confidence interval = 0.09–0.56). No association was found between the T-1514C polymorphism and AIH-1. The onset age of AIH-1 was also accelerated among −1993TT homozygotic individuals ( p = 0.013). The fractions of T-bet positive Th1 cells in the -1993TT homozygotes were 2.2-fold higher than those in -1993CC homozygotes ( p = 0.002). Our results suggest that the T-1993C polymorphism in the TBX21 promoter influences susceptibility to AIH-1 in a Chinese population.