Association analysis of common variants of STAT6, GATA3, and STAT4 to asthma and high serum IgE phenotypes
| Autor: | Riikka Kinos, Tarja Laitinen, Mikko Hurme, Juha Kere, Maritta Kilpeläinen, Lauri A. Laitinen, Sanna Valkonen, Riitta Lahesmaa, Jussi Karjalainen, Pia Rydman, Markku S. Nieminen, Maritta Pykäläinen |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Adult
dbSNP Genotype Immunology Population Single-nucleotide polymorphism GATA3 Transcription Factor Immunoglobulin E Polymorphism Single Nucleotide Atopy Cohort Studies 03 medical and health sciences 0302 clinical medicine medicine Immunology and Allergy Humans education STAT4 Finland 030304 developmental biology Genetic association Genetics 0303 health sciences education.field_of_study biology Haplotype Middle Aged STAT4 Transcription Factor medicine.disease Asthma 3. Good health DNA-Binding Proteins Phenotype Haplotypes Case-Control Studies biology.protein Trans-Activators STAT6 Transcription Factor 030215 immunology Signal Transduction |
| Zdroj: | The Journal of allergy and clinical immunology. 115(1) |
| ISSN: | 0091-6749 |
| Popis: | Background Immune responses characterized by T H 2 type cells and IgE are important for the development of asthma and atopy. The transcription factors STAT6, GATA3, and STAT4 mediate the cytokine-induced development of naive CD4 + T cells into either T H 1 or T H 2 type. Objective We studied genetic variation of the STAT6, GATA3, and STAT4 genes and examined whether single nucleotide polymorphisms (SNPs) in these loci were associated with asthma or serum high IgE levels in the Finnish asthmatic families. Methods With denaturing high-performance liquid chromatography we screened all exons and exon-intron boundaries of the genes in 14 to 22 patients. All identified SNPs were genotyped in 120 nuclear families, and the haplotypes were analyzed by Haplotype Pattern Mining based statistical analysis. When potential association was observed, the analysis was replicated among 245 asthmatic patients and 405 population-based control subjects. Results A total of 23 SNPs were identified, of which 8 were not previously listed in the SNP database. Interestingly, a haplotype analysis of GATA3 showed 3 related haplotypes that associated with different asthma and atopy related phenotypes among both the family and case-control data sets. For STAT6 and STAT4, no significant association to asthma or serum total IgE levels was observed. Conclusions We identified a panel of novel SNPs in genes coding for proteins important in the T H 1/T H 2 cell differentiation. SNPs of the GATA3 gene showed an initial association to asthma-related phenotypes. Elucidation of the importance of the identified panel of SNPs in other T H 1/T H 2 mediated diseases will be of great interest. |
| Databáze: | OpenAIRE |
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