Association of TBX21 promoter polymorphisms with type 1 autoimmune hepatitis in a Chinese population.
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.
Chen
Song
S
Institute of Infectious Diseases, Southwest Hospital, the Third Military Medical University, Chongqing, China.
Zhao
Wenli
W
Tan
Wenting
W
Luo
Xiao
X
Dan
Yunjie
Y
You
Zhonglan
Z
Kuang
Xuemei
X
Wang
Yuming
Y
Deng
Guohong
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D019693:Hepatitis, Autoimmune / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D016019:Survival Analysis; D020825:T-Box Domain Proteins / Q000235:genetics*; D018417:Th1 Cells; D055815:Young Adult; D000098815:T-bet Transcription Factor
D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor