Although there are several reports on the association of RANTES promoter polymorphisms (-403G/A and -28C/G) with asthma, the association of these polymorphisms with atopic dermatitis has not yet been confirmed in other populations.
Our data suggest that -28 C/G and -403 G/A polymorphisms within the RANTES promoter region play an important role in asthma predisposition and in the severity of airway obstruction.
We studied 61 patients with asthma and/or atopy and 129 to 157 newborn controls for the -403 RANTES, -28 RANTES, and -1055 IL-13 SNPs, as well as 47 patients and 60 newborn controls for the -444 LTC4S SNP.
Asthma is a complex inherited disease.The study was undertaken to identify the association of RANTES promoter polymorphisms with atopy and asthma using family-based association tests (FBATs) and generation-specific case-control analyses.
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.
It was previously reported that the gain-of-function -28 guanine allele of the promoter single nucleotide polymorphism (SNP; cytosine to guanine substitution of nucleotide -28 (-28C>G)) in the CC chemokine ligand 5 gene (CCL5) was associated with susceptibility to late-onset asthma in patients who developed asthma at age > or =40 yrs.
Previous studies revealed that polymorphisms of RANTES were implicated in susceptibility to asthma, but a large number of studies reported apparently conflicting results.
The promoter polymorphisms in the RANTES gene did not have a detectable effect on the susceptibility to asthma or allergy or on the blood eosinophil count.
A number of studies have evaluated the functional polymorphism -28C/G in the RANTES promoter region, which had been found to affect the transcription of the RANTES gene, in relation to asthma susceptibility.
Role of the extracellular signal-regulated kinase 1/2 signaling pathway in regulating the secretion of bronchial smooth muscle cells in a rat model of chronic asthma.
Taken together, these findings suggest that eosinophils play a crucial role in the pathogenesis, particularly in eosinophil and T lymphocyte recruitment into the inflamed sites in asthma through RANTES production.
RANTES was also expressed in the bronchial epithelium in vivo, as indicated by positive immunocytochemical staining of bronchial biopsy tissues obtained from mild asthmatic patients before and after treatment with 500 micrograms of inhaled beclomethasone dipropionate (BDP) twice daily or matched placebo for 4 mo.
We have evaluated the effects of doses ranging from 10 ng to 100 micro g of two CC chemokine receptor antagonists, Met-RANTES/CC chemokine ligand 5 (CCL5) and aminooxypentane-RANTES/CCL5, in preventing inflammation in the OVA-sensitized murine model of human asthma.
It was previously reported that the gain-of-function -28 guanine allele of the promoter single nucleotide polymorphism (SNP; cytosine to guanine substitution of nucleotide -28 (-28C>G)) in the CC chemokine ligand 5 gene (CCL5) was associated with susceptibility to late-onset asthma in patients who developed asthma at age > or =40 yrs.