Several whole-genome association studies have shown a significant link between childhood asthma and the 17q12 chromosome region. We selected tagging single nucleotide polymorphisms (SNPs) in the ORMDL3 gene (17q12) to investigate gene variability in relation to adult allergic asthma and asthma/atopy traits in a Czech Caucasian population of adults. We conducted a case-control association study comprising 668 unrelated subjects (337 asthmatic and 331 control subjects). Four selected SNPs (rs17608925, rs12603332, rs8076131, and rs3169572) were genotyped using the TaqMan SNP Genotyping Assays. The single locus analysis showed only a borderline association between rs3169572 variant and asthma (p = 0.030, p(corr) > 0.05). However, seven different haplotypes were identified; among them, the TTAA haplotype was marginally associated with asthma (p = 0.045, p(corr) > 0.05) and TCAG haplotype was significantly associated with asthma in males (p = 0.009, p(corr) < 0.05, odds ratio = 1.48, 95% confidence interval = 1.10-2.00). In addition, associations between the ORMDL3 genotypes and the total IgE level (p = 0.05, p(corr) > 0.05) and hypersensitivity to the pollen (p = 0.007, p(corr) < 0.05) were established. However, no relationship between ORMDL3 SNPs and the pulmonary functions was found (p > 0.05). These findings suggest that the genetic variability in the 17q21 region may be one of the risk factors also for adult asthma, especially in male individuals.

• MeSH
• běloši MeSH
• bronchiální astma epidemiologie   genetika   imunologie   MeSH
• časná přecitlivělost epidemiologie   genetika   imunologie   MeSH
• dospělí MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• genetické lokusy MeSH
• genotyp MeSH
• haplotypy MeSH
• imunoglobulin E biosyntéza   imunologie   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidské chromozomy, pár 17 chemie   genetika   MeSH
• membránové proteiny genetika   MeSH
• mladiství MeSH
• odds ratio MeSH
• rizikové faktory MeSH
• studie případů a kontrol MeSH
• vazebná nerovnováha MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: Eosinophil peroxidase (EPO) gene codes a cationic protein released from the specific granules of activated eosinophils. Eosinophil granulocytes play a central role in the protection of organisms against parasites. They are also regarded as key effector cells in allergic inflammation. We attempted to determine the polymorphisms in the EPO gene typical for the Czech population and to analyze their associations with allergic rhinitis and its intermediary phenotypes. METHODS: We sequenced all 12 exons of the EPO gene, and selected variants were subsequently analyzed by polymerase chain reaction and restriction fragment length polymorphism methods in a case-control study comprising a total of 613 subjects (319 controls and 294 patients with rhinitis). RESULTS: In total, 5 polymorphisms (-1710T/C and -1710T/CTCC, 2649T/C, 3097A/G and 3979A/G) were found in the EPO gene. Polymorphisms 2649T/C and 3097A/G were in complete linkage disequilibrium (D' = 1 for both groups), and both of them were in a strong disequilibrium with the 3979A/G variant (D' = 0.801 for controls, D' = 0.848 for rhinitics). Consequently, these 3 polymorphisms were studied in association with the allergic phenotype. In a single locus analysis, only 3979A/G single nucleotide polymorphism was marginally significantly associated with rhinitis (p = 0.030, p(corr )> 0.05). This polymorphism also showed a marginal association with total serum IgE levels (log(e) IgE, mean +/- SD: genotypes GG = 2.60 +/- 1.20; GA = 2.47 +/- 1.88; AA = 2.38 +/- 1.49; p < 0.05). Furthermore, significant differences in haplotype frequencies between patients and healthy subjects were observed (p < 0.05). CONCLUSIONS: Our study supports the hypothesis that genetic variability in the EPO gene may contribute to the susceptibility to allergic rhinitis (or related phenotypes) in the Czech population. (c) 2009 S. Karger AG, Basel.

• MeSH
• celoroční alergická rýma epidemiologie   genetika   MeSH
• dospělí MeSH
• eosinofilní peroxidasa genetika   MeSH
• frekvence genu genetika   MeSH
• genotyp MeSH
• heterozygot MeSH
• homozygot MeSH
• imunoglobulin E krev   MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• kouření epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• odds ratio MeSH
• rizikové faktory MeSH
• sezónní alergická rýma epidemiologie   genetika   MeSH
• studie případů a kontrol MeSH
• vazebná nerovnováha genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH