Association study of 15 novel single-nucleotide polymorphisms of the T-bet locus among Finnish asthma families

• Published in: Clinical and experimental allergy 2004-07, Vol.34 (7), p.1049-1055
• Main Authors: Ylikoski, E., Kinos, R., Sirkkanen, N., Pykäläinen, M., Savolainen, J., Laitinen, L. A., Kere, J., Laitinen, T., Lahesmaa, R.
• Format: Article
• Language: English
• Subjects: Allergic diseases; asthma; Asthma - genetics; Asthma - immunology; Biological and medical sciences; Chi-Square Distribution; Female; Finland; Fundamental and applied biological sciences. Psychology; Fundamental immunology; human; Humans; Immunoglobulin E - blood; Immunopathology; Linkage Disequilibrium; Male; Medical sciences; Medicin och hälsovetenskap; Polymorphism, Single Nucleotide; SNP; T-bet; T-Box Domain Proteins; Th1/Th2 cells; transcription factors; Transcription Factors - genetics; Transcription Factors - immunology
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/j.1365-2222.2004.01995.x

Summary 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. 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.