title: The -403 G-->A promoter polymorphism in the RANTES gene is associated with atopy and asthma.
abstract: Asthma is a complex inflammatory condition often associated with bronchial hyperreactivity and atopy. Genetic and environmental factors are implicated and several candidate genes have been implicated. Of these, the chemokine RANTES is responsible for the recruitment of inflammatory cells such as eosinophils and T-lymphocytes. We have recently identified a polymorphism within the RANTES promoter (-403 G-->A) and have examined its role, using a PCR-RFLP assay, in the development of atopy and asthma in 201 Caucasian subjects. Atopic status was determined using skin prick testing and serum IgE levels. Severity of airway dysfunction was assessed using spirometric measurement (FEV1) and methacholine challenge (PC20). The -403 A allele was associated with an increased susceptibility to both atopy and asthma. Thus, the proportion of subjects carrying this allele was higher in each of atopic non-asthmatics, non-atopic asthmatics and atopic asthmatics compared with non-atopic, non-asthmatic controls. In particular, this allele was associated with skin test positivity but not IgE level. Homozygosity for the -403 A allele conferred a 6.5-fold increased risk of moderate/severe airway obstruction (FEV1 < or = 80% predicted), a marker for established asthma. Our data, whilst preliminary, indicate that the association of RANTES genotype with both atopy and asthma reflect independent effects, suggesting different mechanisms for the role of this chemokine in atopy and development of airway obstruction.
authors.affiliation: Lung Injury and Inflammation Group, Centre for Cell & Molecular Medicine, Keele University, North Staffordshire Hospital, UK.
authors.forename: A A
authors.initials: AA
authors.lastname: Fryer
authors.forename: M A
authors.initials: MA
authors.lastname: Spiteri
authors.forename: A
authors.initials: A
authors.lastname: Bianco
authors.forename: M
authors.initials: M
authors.lastname: Hepple
authors.forename: P W
authors.initials: PW
authors.lastname: Jones
authors.forename: R C
authors.initials: RC
authors.lastname: Strange
authors.forename: R
authors.initials: R
authors.lastname: Makki
authors.forename: G
authors.initials: G
authors.lastname: Tavernier
authors.forename: F I
authors.initials: FI
authors.lastname: Smilie
authors.forename: A
authors.initials: A
authors.lastname: Custovic
authors.forename: A A
authors.initials: AA
authors.lastname: Woodcock
authors.forename: W E
authors.initials: WE
authors.lastname: Ollier
authors.forename: A H
authors.initials: AH
authors.lastname: Hajeer
mesh_terms: D000225:Adenine; D000328:Adult; D000402:Airway Obstruction / Q000235:genetics / Q000276:immunology; D001249:Asthma / Q000235:genetics* / Q000276:immunology; D018946:Chemokine CCL5 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006147:Guanine; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics* / Q000276:immunology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: D018946:Chemokine CCL5; D006147:Guanine; D000225:Adenine