Toll-like receptor 4 polymorphism and severity of atopy in asthmatics.
Genes Immun
; 5(1): 41-5, 2004 Jan.
Article
de En
| MEDLINE
| ID: mdl-14735148
ABSTRACT
Endotoxin exposure may have a protective effect against asthma and atopy. An Asp299Gly polymorphism in the Toll-like receptor 4 (TLR4) gene reduces responsiveness to endotoxin. This study determined the effect of TLR4 polymorphism on the risk and severity of asthma and atopy. In all, 336 UK Caucasian families with > or = 2 affected sibs (physician's diagnosis of asthma and current medication use) and 179 Caucasians without asthma or a family history of asthma were genotyped using ARMS-PCR. No association of the TLR4 polymorphism was found with the risk of developing asthma, either in parent-affected sibling trios, or in case-control analyses (P>0.05). In the first affected asthmatic siblings, the atopy severity score (based on size and number of positive skin-prick tests and specific IgE) was higher in those with the Asp/Gly or Gly/Gly genotypes (mean 1.8, s.d. 1.1, n=39) compared to those with the Asp/Asp genotype (mean 1.2, s.d. 1.0, n=279) (P=0.003, t-test). No associations were found with total IgE, FEV(1) % predicted, slope of FEV(1) response to methacholine or asthma severity score (P>0.05). This study confirms the previously observed lack of association of TLR4 polymorphisms with asthma. In contrast, the findings suggest that genetically determined hyporesponsiveness to endotoxin may increase atopy severity.
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Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Polymorphisme génétique
/
Asthme
/
Glycoprotéines membranaires
/
Récepteurs de surface cellulaire
Type d'étude:
Prognostic_studies
Limites:
Female
/
Humans
/
Male
Langue:
En
Journal:
Genes Immun
Sujet du journal:
ALERGIA E IMUNOLOGIA
/
BIOLOGIA MOLECULAR
Année:
2004
Type de document:
Article
Pays d'affiliation:
Royaume-Uni