Association study of 15 novel single‐nucleotide polymorphisms of the T‐bet locus among Finnish asthma families
- 9 July 2004
- journal article
- Published by Wiley in Clinical and Experimental Allergy
- Vol. 34 (7) , 1049-1055
- https://doi.org/10.1111/j.1365-2222.2004.01995.x
Abstract
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™ 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. 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.Keywords
This publication has 28 references indexed in Scilit:
- A Major Susceptibility Gene for Asthma Maps to Chromosome 14q24American Journal of Human Genetics, 2002
- Association of the ADAM33 gene with asthma and bronchial hyperresponsivenessNature, 2002
- T-bet is a STAT1-induced regulator of IL-12R expression in naïve CD4+ T cellsNature Immunology, 2002
- Qualitative and quantitative analysis of mRNA associated with four putative splicing mutations (621+3A→G, 2751+2T→A, 296+1G→C, 1717–9T→C-D565G) and one nonsense mutation (E822X) in the CFTR geneHuman Genetics, 2001
- Human Population Genetics: Lessons from FinlandAnnual Review of Genomics and Human Genetics, 2001
- A Single Point Mutation at the 3′-Untranslated Region of Ran mRNA Leads to Profound Changes in Lipopolysaccharide Endotoxin-mediated ResponsesPublished by Elsevier ,2001
- Population genetics—making sense out of sequenceNature Genetics, 1999
- Large-Scale Identification, Mapping, and Genotyping of Single-Nucleotide Polymorphisms in the Human GenomeScience, 1998
- Detection of Single-Nucleotide Polymorphisms with the WAVE™ DNA Fragment Analysis SystemGenetic Testing, 1997
- Interleukin 12 inhibits antigen-induced airway hyperresponsiveness, inflammation, and Th2 cytokine expression in mice.The Journal of Experimental Medicine, 1995