Functional polymorphisms in TBX21 and HLX are associated with development and prognosis of Graves' disease.
BACKGROUND
It has been indicated that T-box 21 (TBX21) and H 2.0-like homeobox (HLX) are transcription factors related to the differentiation of T helper 1 cells, whereas GATA-binding protein 3 is the master transcription factor of T helper 2 cells.


METHODS
We genotyped -1514T/C (rs17250932) and -1993T/C (rs4794067) polymorphisms of TBX21, - 742C/G polymorphism (rs2184658) of HLX and -1420G/A polymorphism (rs1269486) of GATA3 in genomic DNA samples from Japanese patients; 51 patients with severe Hashimoto's disease (HD), 39 with mild HD, 66 with intractable Graves' disease (GD), in whom remission was difficult to induce, 47 with GD in remission and 79 healthy volunteers.


RESULTS
The T alleles of the TBX21-1514T/C and -1993T/C polymorphisms were more frequent in patients with intractable GD than in those with GD in remission. Among individuals with the TBX21-1993TT genotype, the G allele of HLX-742C/G polymorphism, which correlates with low HLX expression, was more frequent in patients with intractable GD than in those with GD in remission.


CONCLUSIONS
Functional polymorphisms in TBX21 are associated with the development of autoimmune thyroid diseases and prognosis of GD, and a functional polymorphism in HLX in combination with the TBX21 polymorphism is also associated with the prognosis of GD.
Department of Biomedical Informatics, Division of Health Sciences, Osaka University Graduate School of Medicine, Osaka, Japan.
Mami
M
Morita
Mikio
M
Watanabe
Naoya
N
Inoue
Chisa
C
Inaoka
Takashi
T
Akamizu
Ke-Ita
KI
Tatsumi
Yoh
Y
Hidaka
Yoshinori
Y
Iwatani
D000328:Adult; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006111:Graves Disease / Q000175:diagnosis / Q000235:genetics*; D050031:Hashimoto Disease / Q000175:diagnosis / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D020825:T-Box Domain Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult; D000098815:T-bet Transcription Factor
C084058:HLX protein, human; D018398:Homeodomain Proteins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors