Association study of 15 novel single-nucleotide polymorphisms of the T-bet locus among Finnish asthma families.
OBJECTIVE
T-box expressed in T cells (T-bet) is a transcription factor regulating the commitment of T helper (Th) cells by driving the cells into the Th1 direction. Abnormal Th1/Th2 balance may lead to complex disorders like asthma or autoimmune diseases. Recent studies have suggested that T-bet might be a candidate gene for asthma. This led us to screen 23 Finnish individuals for single-nucleotide polymorphisms (SNPs) in the T-bet locus and study the association between the SNPs and high serum IgE level and asthma.


METHODS
We screened all six exons, adjacent intronic areas and 2 kb of the 5'-flanking region from 23 individuals utilizing WAVE trade mark technology. To explore whether T-bet is associated in serum IgE regulation or asthma we genotyped the SNPs in a Finnish asthmatic founder population. The association analyses were made using haplotype pattern mining.


RESULTS
Fifteen novel SNPs were found in the T-bet gene. Within the Finnish asthmatic founder population, there was no association between T-bet SNPs and high serum IgE level or asthma.


CONCLUSIONS
The genetic variability in the T-bet gene does not play a role in the pathogenesis of human asthma. Our results provide a novel panel of SNPs in T-bet and will help determine whether the SNPs have a functional role in other T cell-mediated diseases.
Ylikoski
E
E
Centre for Biotechnology, University of Turku and Abo Akademi University, Finland. emmi.ylikoski@btk.utu.fi
Kinos
R
R
Sirkkanen
N
N
Pykäläinen
M
M
Savolainen
J
J
Laitinen
L A
LA
Kere
J
J
Laitinen
T
T
Lahesmaa
R
R
D001249:Asthma / Q000235:genetics* / Q000276:immunology; D016009:Chi-Square Distribution; D005260:Female; D005387:Finland; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D020825:T-Box Domain Proteins; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology; D000098815:T-bet Transcription Factor
D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D007073:Immunoglobulin E