Ryu, H. J., Jung, H. Y., Park, J. S., Ryu, G. M., Heo, J. Y., Kim, J. J. et al. Gene-based single nucleotide polymorphisms and linkage disequilibrium patterns of 29 asthma candidate genes in the chromosome 5q31-33 region in Koreans. Int. Arch. Allergy Immunol. 139, 209-216
Numerous genetic studies have mapped asthma susceptibility genes to a region on chromosome 5q31-33 in several populations. This region contains a cluster of cytokines and other immune-related genes important in immune response. In the present study, to determine the genetic variations and patterns of linkage disequilibrium (LD), we resequenced all the exons and promoter regions of the 29 asthma candidate genes in the chromosome 5q31-33 region.
We identified a total of 314 genetic variants, including 289 single nucleotide polymorphisms (SNPs), 22 insertion/deletion polymorphisms and 3 microsatellites. Standardized variance data for allele frequency revealed substantial differences in SNP allele frequencies among different ethnic groups. Interestingly, significant ethnic differences were observed mainly in intron SNPs. LD block analysis using 174 common SNPs with a frequency of >10% disclosed strong LD within most candidate genes. No significant LD was observed across genes, except for one LD block (CD14-IK block). Gene-based haplotype analyses showed that 1-5 haplotype-tagging SNPs may be used to define the six or fewer common haplotypes with a frequency of >5%, regardless of the number of SNPs.
Overall, our results provide useful information for the identification of immune-mediated disease genes in the chromosome 5q31-33 region, as well as valuable evidence for gene-based haplotype analysis in disease association studies.
[Show abstract][Hide abstract] ABSTRACT: Much attention has been given in this report to the potential fallacies of skin tests in the diagnosis of allergies of the immediate type. Yet after 100 years, skin tests are still a valuable diagnostic tool for the allergist. It is essential, however, to avoid the pitfall of placing too much emphasis on either the positive or negative skin test. No test, whether in vivo or in vitro, old or newly developed, provides the final diagnosis. To hand the patient a list of inhalants and foods to which he or she is 'allergic' based solely on positive skin tests is indefensible. The physician needs a thorough knowledge of his patient. Any diagnostic test, including skin testing, must be interpreted in the clinical light, in terms of the history and physical examination.
Medical Clinics of North America 02/1974; 58(1):55-63. · 2.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: While asthma is considered an inflammatory disorder of the conducting airways, it is becoming increasingly apparent that the disease is heterogeneous with respect to immunopathology, clinical phenotypes, response to therapies, and natural history. Once considered purely an allergic disorder dominated by Th2-type lymphocytes, IgE, mast cells, eosinophils, macrophages, and cytokines, the disease also involves local epithelial, mesenchymal, vascular and neurologic events that are involved in directing the Th2 phenotype to the lung and through aberrant injury-repair mechanisms to remodeling of the airway wall. Structural cells provide the necessary "soil" upon which the "seeds" of the inflammatory response are able to take root and maintain a chronic phenotype and upon which are superimposed acute and subacute episodes usually driven by environmental factors such as exposure to allergens, microorganisms, pollutants or caused by inadequate antiinflammatory treatment. Greater consideration of additional immunologic and inflammatory pathways are revealing new ways of intervening in the prevention and treatment of the disease. Thus increased focus on environmental factors beyond allergic exposure (such as virus infection, air pollution, and diet) are identifying targets in structural as well as immune and inflammatory cells at which to direct new interventions.
[Show abstract][Hide abstract] ABSTRACT: Although it has been recognised that genetics plays an important role in the development of asthma, important causal loci remain to be identified. The aim of the present study was to examine the association of known and novel candidate genes with asthma. Two independent samples, including 170 asthmatic cases and 347 controls in the initial sample, and 202 asthmatic cases and 332 controls in the confirmation sample, were recruited from the same region of China. Functional single nucleotide polymorphisms (SNPs; n = 129) from 105 genes were genotyped using MassARRAY technology, and 119 SNPs were used for the subsequent analysis. In the initial sample, three SNPs, rs320995 in the cysteinyl leukotriene receptor 1 gene, rs1047266 in the tumour necrosis factor receptor superfamily, member 10b, gene and rs40401 in the interleukin-3 gene, were associated with risk of asthma. Notably, under the recessive genetic model, subjects without the thymidine allele in SNP rs320995 had a 3.1 times higher risk of asthma, which remained significant after accounting for multiple testing. This association was replicated in the confirmation sample and validated by meta-analysis. Further, sex-specific analysis was performed, but no sex difference was found. The present study provided coherent evidence that cysteinyl leukotriene receptor 1 gene variation is associated with risk of asthma.
European Respiratory Journal 11/2008; 33(1):42-8. DOI:10.1183/09031936.00057708 · 7.64 Impact Factor
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