Asthma

Busse, William W.; Lemanske, Robert F.

doi:10.1056/nejm200102013440507

Cited by 1,721 publications

(1,312 citation statements)

References 90 publications

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“…19 While also involved in host defense against bacterial infection, the mast cell plays a pivotal role in the pathogenesis of human asthma. 20,21 We tested the association of asthma with the only common (allelic frequency X10% in each of our ethnic populations), non-synonymous TLR6 SNP (Ser249Pro). This nonconservative amino-acid change occurs in the extracellular domain of the TLR6 protein sequence in a region that is homologous and conserved in the mouse.…”

Section: Resultsmentioning

confidence: 99%

Toll-like receptor 6 gene (TLR6): single-nucleotide polymorphism frequencies and preliminary association with the diagnosis of asthma

et al. 2004

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Toll-like receptor 6 (TLR6) is one of a series of highly conserved innate immune receptors. We resequenced TLR6 in DNA samples from 24 African Americans, 23 European Americans, and 24 Hispanic Americans, identifying 53 SNPs, 22 with an allele frequency 45%. Significant differences in SNP frequencies among the three populations were noted. In all, 11 SNPs caused amino-acid changes, including one with a frequency 45% in all three populations. Utilizing this SNP (Ser249Pro), we performed exploratory nested case-control disease-association studies, including one involving 56 African Americans with asthma and 93 African American controls. The minor allele of this SNP was associated with decreased risk for asthma (odds ratio 0.38, 95% CI 0.16-0.87, P ¼ 0.01), an effect consistent with the known biology of the toll-like receptors. Although replication of this finding in other, larger samples is needed, variation in TLR6 may have relevance to the pathogenesis of immunologically mediated diseases.

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Section: Resultsmentioning

confidence: 99%

Toll-like receptor 6 gene (TLR6): single-nucleotide polymorphism frequencies and preliminary association with the diagnosis of asthma

et al. 2004

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“…All patients with asthma have a specific pattern of inflammation in the airways that is characterized by degranulated mast cells, an infiltration of eosinophils, and an increased number of activated T-helper 2 cells (see Glossary) (1). It is believed that this specific pattern of inflammation underlies the clinical features of asthma, including intermittent wheezing, dyspnea, cough, and chest tightness.…”

Section: The Molecular Basis Of Inflammation In Asthmamentioning

confidence: 99%

How Do Corticosteroids Work in Asthma?

2003

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“…1,2 The importance of T H 2 cytokines and T H 1/T H 2 balance in asthma is well recognized in patients and animal models. 3,4 Interleukin 4 (IL-4) exerts its major role in T H 2 differentiation, an initial step in IgE mediated immunity.…”

Section: Introductionmentioning

confidence: 99%

Local adaptation and population differentiation at the interleukin 13 and interleukin 4 loci

et al. 2004

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A 25.6 kb region at chromosome 5q31, covering the entire human interleukin 13 (IL-13) and interleukin 4 (IL-4) genes, has been reported to be associated with bronchial asthma. We have examined nucleotide variations at this locus in African, European American, and Japanese populations, using 120 diallelic variants. A block of strong linkage disequilibrium (LD) (|D 0 |40.7) spans a 10 kb region containing IL-4 in European American and Japanese populations, and is present but less clear in African samples. Two major haplotypes at IL-4 account for 480% of haplotypes in European Americans and Japanese. These haplotypes are common and quite diverged from each other and the ancestral haplotype, resulting in highly significant deviations from neutrality. F ST statistics show that European American and Japanese populations are unusually distinct at the IL-4 locus. The most common haplotype in the European American population is much less common in the Japanese population, and vice versa. This implies that natural selection has acted on IL-4 haplotypes differently in different populations. This selected variation at IL-4 may account for some genetic variance underlying susceptibility to asthma and other allergic diseases. The strong LD observed in the IL-4 region may allow more efficient disease-association studies using this locus.

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Asthma

Cited by 1,721 publications

References 90 publications

Toll-like receptor 6 gene (TLR6): single-nucleotide polymorphism frequencies and preliminary association with the diagnosis of asthma

Toll-like receptor 6 gene (TLR6): single-nucleotide polymorphism frequencies and preliminary association with the diagnosis of asthma

How Do Corticosteroids Work in Asthma?

Local adaptation and population differentiation at the interleukin 13 and interleukin 4 loci

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