Mapping oligogenes for atopy and asthma by meta-analysis

Collins, Andrew; Ennis, Sarah; Tapper, William; Morton, N. E.

doi:10.1590/s1415-47572000000100001

Cited by 16 publications

(16 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In conclusion, these results indicate that the MHC gene region, possibly MHC class II genes, influence the specific IgE response in the horse and that more than one class II locus might affect the specific allergen response, as has been suggested in humans [4]. A better characterisation of the equine MHC and a finer genetic map of ECA-20, as well as the identification of the relevant epitopes on the recombinant allergens will allow us to understand the mechanisms underlying the uncovered association between the equine MHC gene region and specific IgE levels.…”

Section: Discussionsupporting

confidence: 68%

Association between the MHC gene region and variation of serum IgE levels against specific mould allergens in the horse

et al. 2003

View full text Add to dashboard Cite

-To investigate whether the equine major histocompatibility complex (MHC) gene region influences the production of mould-specific immunoglobulin E antibodies (IgE), alleles of the equine leukocyte antigen (ELA-A) locus and three microsatellite markers (UM-011, HTG-05 and HMS-42) located on the same chromosome as the equine MHC were determined in 448 Lipizzan horses. Statistical analyses based on composite models, showed significant associations of the ELA-A and UM-011 loci with IgE titres against the recombinant Aspergillus fumigatus 7 antigen (rAsp f 7). UM-011 was also significantly associated with IgE titres against the recombinant Aspergillus fumigatus 8 antigen (rAsp f 8). In addition to the loci mentioned above, the MHC class II DQA and DRA loci were determined in 76 Lipizzans from one stud. For IgE levels against rAsp f 7, the composite model showed the strongest association for DQA * Correspondence and reprints E-mail: eliane.marti@itz.unibe.ch S178 I. Curik et al.(P < 0.01) while for rAsp f 8 specific IgE levels, similarly to the results found with all 448 horses, the strongest association was found with UM-011 (P = 0.01), which is closely linked with the MHC class II DRB locus. These results suggest that the equine MHC gene region and possibly MHC class II loci, influence the specific IgE response in the horse. However, although the strongest associations were found with DQA and UM-011, this study did not distinguish if the observed effects were due to the MHC itself or to other tightly linked genes.horse / major histocompatibility complex / immunoglobulin E / specific mould allergen

show abstract

Section: Discussionsupporting

confidence: 68%

Association between the MHC gene region and variation of serum IgE levels against specific mould allergens in the horse

et al. 2003

View full text Add to dashboard Cite

show abstract

“…The identification of variations in specific genes that are involved in mediating the expression of the atopic asthmatic phenotype could lead the field to a specific molecular pathway providing new drug targets. Both physiologic/pharmacologic and genetic studies in animal models and human populations have identified a number of candidate genes and pathways that regulate IgE levels and airway hyperresponsiveness that represent potential new drug targets (10,11). However, the significance of SNPs and other genetic variations in these genes to atopic asthma is still unproven.…”

mentioning

confidence: 99%

“…The most commonly used experimental design was to associate one of several asthma-associated phenotypes (atopy, IgE levels, and bronchial hyperresponsiveness [BHR]) to microsatellite markers or SNPs within specific helper T cell type 2 (Th2) cytokine-or IgE-regulating genes (10,(12)(13)(14). However, none of the linkage studies found loci that meet reasonable criteria for significance (15), and only a few of the association studies reported qualify for possible significance.…”

mentioning

confidence: 99%

Allelic Frequencies and Patterns of Single-nucleotide Polymorphisms in Candidate Genes for Asthma and Atopy in Iceland

Hákonarson

Björnsdóttir²,

Ostermann³

et al. 2001

Am J Respir Crit Care Med

View full text Add to dashboard Cite

Numerous asthma and atopy loci have been reported in studies demonstrating associations of the asthma-related phenotypes atopy, elevated IgE levels, and bronchial hyperresponsiveness with alleles of microsatellite markers and single-nucleotide polymorphisms (SNPs) within specific cytokine/chemokine and IgE-regulating genes. Although the studies reporting these observations are compelling, most of them lack statistical power. We assessed the nature, pattern, and frequency of SNPs in 24 candidate genes in Iceland and looked for associations with asthma and atopy. We identified 42 SNPs with an average minor allele frequency of 20.3% (asthma) and 20.7% (control). Twenty SNPs (48%) were within coding sequences and 90% of those led to a predicted change in protein sequence. No differences were detected in the allelic frequencies of SNPs in any of these candidate genes between control subjects and the patients with atopic asthma. Moreover, linkage analysis that included 269 patients with atopic asthma uncovered no evidence of linkage to markers associated with these genes. We conclude that this study has failed to produce evidence in support of the notion that variations within these 24 candidate atopy and asthma genes significantly influence the expression of the atopic asthmatic phenotype or contribute to the susceptibility of atopic asthma.

show abstract

“…The only common denominator is a nominal significance level, which is usually not specified unless it lies beyond an arbitrary threshold. Such material, although peer-reviewed, is subject to many errors and biases but can be used to define candidate regions (1).…”

mentioning

confidence: 99%

A first trial of retrospective collaboration for positional cloning in complex inheritance: Assay of the cytokine region on chromosome 5 by the Consortium on Asthma Genetics (COAG)

Lonjou

Barnes

Chen

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The central problem of complex inheritance is to map oligogenes for disease susceptibility, integrating linkage and association over samples that differ in several ways. Combination of evidence over multiple samples with 1,037 families supports loci contributing to asthma susceptibility in the cytokine region on 5q [maximum logarithm of odds (lod) ‫؍‬ 2.61 near IL-4], but no evidence for atopy. The principal problems with retrospective collaboration on linkage appear to have been solved, providing far more information than a single study. A multipoint lod table evaluated at commonly agreed reference loci is required for both collaboration and metaanalysis, but variations in ascertainment, pedigree structure, phenotype definition, and marker selection are tolerated. These methods are invariant with statistical methods that increase the power of lods and are applicable to all diseases, motivating collaboration rather than competition. In contrast to linkage, positional cloning by allelic association has yet to be extended to multiple samples, a prerequisite for efficient combination with linkage and the greatest current challenge to genetic epidemiology. T he central problem of complex inheritance is to map oligogenes for disease susceptibility. Even the largest study has low power to map genes of small effect by the complementary methods of linkage and allelic association, and a confirmatory sample is necessary even for genes of large effect. Often the significance of multiple samples is controversial. These considerations favor combination of evidence, for which there are three approaches called meta-analysis, prospective collaboration, and retrospective collaboration.Meta-analysis typically uses published summaries and so is comprehensive. It would be the method of choice if publication did not favor positive results and the data were summarized in a way that distinguishes information, effect, and location, like lod scores for major loci. Unfortunately, studies of complex inheritance differ widely in phenotype definition, selection of families or cases and controls, choice of marker loci, and statistical analysis. The only common denominator is a nominal significance level, which is usually not specified unless it lies beyond an arbitrary threshold. Such material, although peer-reviewed, is subject to many errors and biases but can be used to define candidate regions (1).Prospective collaboration is typified by national consortia like the Collaborative Study on the Genetics of Asthma (2). Each member of the consortium tries to follow the same protocol, including phenotype definitions, sampling scheme, and markers. This effort assures uniformity but makes no use of the many studies with different but equally defensible protocols.Retrospective collaboration is typified by the international Consortium on Asthma Genetics (COAG). Each member of the consortium provides data published independently with no agreement about protocol. The analysis must be coherent, or else would be no more than a meta-analysis of a subse...

show abstract

Mapping oligogenes for atopy and asthma by meta-analysis

Cited by 16 publications

References 44 publications

Association between the MHC gene region and variation of serum IgE levels against specific mould allergens in the horse

Association between the MHC gene region and variation of serum IgE levels against specific mould allergens in the horse

Allelic Frequencies and Patterns of Single-nucleotide Polymorphisms in Candidate Genes for Asthma and Atopy in Iceland

A first trial of retrospective collaboration for positional cloning in complex inheritance: Assay of the cytokine region on chromosome 5 by the Consortium on Asthma Genetics (COAG)

Contact Info

Product

Resources

About