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

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 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.