المؤلفون: Waltraud Eder, Dennis Nowak, Charlotte Braun-Fahrländer, Fernando D. Martinez, Walter T. Klimecki, Josef Riedler, Lizhi Yu, Erika von Mutius

المصدر: Journal of Allergy and Clinical Immunology. 116:601-607

مصطلحات موضوعية: Male, Immunology, Lipopolysaccharide Receptors, Biology, Immunoglobulin E, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Atopy, Polymorphism (computer science), Immunopathology, Genotype, medicine, Animals, Humans, Immunology and Allergy, Allele, Gene–environment interaction, Child, Promoter Regions, Genetic, Dust, Environmental Exposure, Environmental exposure, medicine.disease, Endotoxins, Animals, Domestic, biology.protein

الوصف: Background Most complex diseases are the result of interactions between polymorphisms in the genome and environmental exposures. Objective We sought to investigate the previously reported association between a polymorphism in the promoter region of CD14 ( CD14/−260C→T ) and serum IgE levels in relation to the environment to which children are exposed. Methods In 624 children living in 2 rural communities in Europe, we compared total and specific serum IgE levels between the genotypes of CD14/−260 in relation to exposure to animals and in relation to house dust endotoxin. Results We found that the C allele of CD14/−260 was associated with higher levels of both total and specific serum IgE to aeroallergens in children with regular contact with pets, whereas an association in the opposite direction was found in children with regular contact with stable animals. This modifying effect of animal exposure was not explained by levels of house dust endotoxin. However, in children with high levels of house dust endotoxin, the C allele was associated with less specific IgE, independently from animal exposure. Conclusion Because CD14 is a pattern recognition receptor for microbial molecules, the results suggest that the type and concentrations of such molecules present in the environment strongly determine the direction of the association between CD14/−260 and serum markers of atopy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::930079d84de07af54682ff2683ab81e7Test
https://doi.org/10.1016/j.jaci.2005.05.003Test

المؤلفون: O Holst, Dennis Nowak, E. von Mutius, Walter T. Klimecki, Lizhi Yu, Fernando D. Martinez, J. Riedler, C Braun-Fahrländer, Waltraud Eder

المصدر: Allergy. 61(9)

مصطلحات موضوعية: Allergy, Bacteria, Immunology, Haplotype, Genetic Variation, Rhinitis, Allergic, Seasonal, Single-nucleotide polymorphism, Agriculture, Biology, Immunoglobulin E, medicine.disease, Asthma, Minor allele frequency, Nod1 Signaling Adaptor Protein, medicine, Immunology and Allergy, Hay fever, Humans, Genetic Predisposition to Disease, Genetic variability, Allele, Child

الوصف: Background: Caspase recruitment domain protein (CARD) 4 has been recently identified as an intracellular pattern recognition receptor that interacts with muropeptides found in common Gram-negative bacteria. We therefore aimed to explore whether the previously observed inverse association between exposure to microbial products and asthma and allergies in childhood is modified by genetic variation in CARD4. Methods: We genotyped 668 children [mean age 9.3 (SD 1.5) years] enrolled in the cross-sectional ALEX study for seven haplotype tagging single nucleotide polymorphisms in CARD4. We studied the association of asthma, hay fever and allergen-specific serum immunoglobulin E with exposure to a farming environment and with levels of endotoxin and muramic acid measured in house dust samples. We tested whether these associations differed between the genotypes of the polymorphisms under study. Results: A strong protective effect of a farming environment on allergies was only found in children homozygous for the T allele in CARD4/−21596, but not in children carrying the minor allele (C). Among the former, farmers’ children had a significantly lower frequency of sensitization against pollen (5.8%), hay fever (1.7%) and atopic asthma symptoms (1.7%) compared with children not living on a farm (19.4%, 13.0% and 7.6%, P

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3b9019749ea31b721463e8593f2b280bTest
https://pubmed.ncbi.nlm.nih.gov/16918516Test

المؤلفون: Valérie Siroux, Walter T. Klimecki, Penelope E. Graves, Fernando D. Martinez, Stefano Guerra

المساهمون: Arizona Respiratory Center, INSERM U823, équipe 12 (Epidémiologie Environnementale appliquée à la Reproduction et la Santé Respiratoire), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Boudier, Anne

المصدر: Journal of Allergy and Clinical Immunology
Journal of Allergy and Clinical Immunology, Elsevier, 2005, 116 (3), pp.650-6. ⟨10.1016/j.jaci.2005.05.004⟩

مصطلحات موضوعية: Hypersensitivity, Immediate, Male, Allergy, Candidate gene, Linkage disequilibrium, MESH: Asthma, MESH: Membrane Glycoproteins, Eczema, MESH: Amino Acid Sequence, Immunoglobulin E, Polymerase Chain Reaction, Linkage Disequilibrium, Atopy, 0302 clinical medicine, MESH: Child, Gene cluster, Immunology and Allergy, Hepatitis A Virus Cellular Receptor 1, Child, Chromatography, High Pressure Liquid, Genetics, 0303 health sciences, Membrane Glycoproteins, biology, MESH: Polymorphism, Single Nucleotide, MESH: Genetic Predisposition to Disease, Protein-Tyrosine Kinases, 3. Good health, MESH: Linkage Disequilibrium, Chromosomes, Human, Pair 5, Receptors, Virus, Female, MESH: Hypersensitivity, Immediate, MESH: Chromosomes, Human, Pair 5, Adolescent, Molecular Sequence Data, Immunology, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, MESH: Protein-Tyrosine Kinases, 03 medical and health sciences, MESH: Skin Tests, medicine, Humans, Genetic Predisposition to Disease, Amino Acid Sequence, Allele, MESH: Chromatography, High Pressure Liquid, Skin Tests, 030304 developmental biology, MESH: Adolescent, MESH: Molecular Sequence Data, MESH: Humans, MESH: Polymerase Chain Reaction, medicine.disease, MESH: Receptors, Virus, Asthma, MESH: Male, MESH: Eczema, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Female, 030215 immunology

الوصف: International audience; BACKGROUND: The T-cell immunoglobulin domain and mucin domain (TIM) gene family and the gene for IL-2-inducible T-cell kinase (ITK), located in chromosome 5 q 33 and potentially involved in the T-cell proliferation and differentiation, are good candidate genes for allergic diseases. OBJECTIVE: We assessed the role of polymorphisms in the TIM family genes and ITK in atopy, eczema, and asthma. METHODS: Twenty-one polymorphisms in the TIM-ITK gene cluster were genotyped in 564 children enrolled in the Tucson Children's Respiratory Study. Skin prick tests to common allergens were performed at age 6.1 years (n=508), age 10.8 years (n=539), and age 16.6 years (n=424). Asthma and eczema were assessed by questionnaire at these 3 points. Averaged relative risks were estimated. RESULTS: One 15-bp insertion/deletion in exon 4 of TIM 1 was significantly related to atopy and eczema (relative risk associated with carrying at least 1 rare allele=1.24 [1.07--1.45], P=.005; and 1.43 [1.01--2.01], P=.004, respectively). The 3 tested single nucleotide polymorphisms (SNPs) in TIM 3 were significantly related to atopy and eczema. One of them, at position +4259 calculated from the translation start site, predicts a putative change in the amino acid sequence of the protein, and was the most strongly related to atopy (relative risk=1.28 [1.12--1.47]; P=.0003). SNPs in the 5' genomic region in ITK, which show moderate linkage disequilibrium with those in TIM 3, had an independent effect on atopy. None of the polymorphisms studied was related to asthma. CONCLUSION: Our findings support a potential role for SNPs in TIM 1, TIM 3, and ITK, independent of each other, in allergic diseases.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a4c9e628015848b0ea36225bccbf92c8Test
https://www.hal.inserm.fr/inserm-00728263Test