Linked Life Data

11281413

Source:http://linkedlifedata.com/resource/pubmed/id/11281413

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-4-2
pubmed:abstractText
The complex etiology of bronchial asthma (BA), one of the most common inflammatory diseases throughout the world, involves a combination of various genetic and environmental factors. A number of investigators have undertaken linkage and association studies to shed light on the genetic background of BA, but the genetic aspects of this disease are still poorly understood. In the course of a project to screen the entire human genome for single nucleotide polymorphisms (SNPs) that might represent useful markers for large-scale association analyses of common diseases and pharmacogenetic traits, we identified six SNPs within the gene encoding I-kappaB-associated protein (IKAP), a regulator of the NF-kappaB signal pathway. Most of these SNPs were in linkage disequilibrium with each other. We observed a strong allelic association between BA in childhood and two of the SNP sites, T3214A (Cys1072Ser) and C3473T (Pro1158Leu); P = 0.000004 for T3214A and P = 0.0009 for C3473T. T3214A was also associated with BA in adult patients (P = 0.000002), but C3473T was not (P = 0.056). To confirm the above results, we compared estimated frequencies of haplotypes of the six SNPs between BA patients and controls. We found a strong association between BA in childhood and a specific haplotype, TGAAAT, that involved two amino-acid substitutions (819T, 2295G, 2446A, 2490A, 3214A, and 3473T; P = 0.00004, odds ratio, 2.94; 95% confidence interval [CI], 2.48-3.4). On the other hand, haplotype TACGTC, which differed from the TGAAAT haplotype in the last five nucleotides, was inversely correlated with the BA phenotype (P = 0.002; odds ratio, 9.83; 95% CI, 8.35-11.31). These results indicated that specific variants of the IKAP gene, or a variant in linkage disequilibrium with the TGAAAT haplotype, might be associated with mechanisms responsible for early-onset BA.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1434-5161
pubmed:author
pubmed:issnType
Print
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
57-63
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Amino-acid substitutions in the IKAP gene product significantly increase risk for bronchial asthma in children.
pubmed:affiliation
Laboratory of Molecular Medicine, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Japan.
pubmed:publicationType
Journal Article