A Functional Polymorphism in the RANTES Gene Promoter Is Associated with the Development of Late-Onset Asthma

Abstract

The CC chemokine regulated upon activation, normal T-cell exsome 17q (5,6), where the gene encoding RANTES is located, the RANTES promoter region (7, 9), whereas another ge-83 middle-onset patients with asthma (onset at 20 to 40 years of netic study found a significant association of the Ϫ403A allele age), and 98 early-onset patients with asthma (onset at less than with atopy and asthma in adults (10). 20 years of age). The Ϫ28G allele was significantly associated with late-onset asthma (odds ratio ϭ 2.033; 95% confidence interval,The age at onset of asthma covers a wide range. Almost in the pathophysiology of asthma that develops in later life Our findings suggest that, among Japanese, the Ϫ28G allele of (12). Furthermore, the age at onset of asthma correlates the RANTES promoter region confers susceptibility to late-onset with reactivity of basophils; early-onset asthma is significantly asthma.associated with greater levels of anti-immunoglobulin E (IgE)-induced histamine release from basophils (13). In a Keywords: late-onset asthma; RANTES; single nucleotide polymorphism previous study, we found that the age at onset of asthma (SNP)

RANTES Gene Promoter Polymorphisms Are Associated with Bronchial Hyperresponsiveness in Korean Children with Asthma

“…In conjunction with this result, the -403A allele was suggested to be associated with an increased susceptibility to both atopy and asthma [16]. However, Hizawa et al [27] reported that the -403A allele was not associated with any of the asthma subgroups, and our results also showed that the RANTES -403 G[A polymorphism was not correlated with asthma susceptibility or asthma-related phenotypes.…”

“…It has also been reported that the -28G allele elevates promoter activity and increase RANTES protein expression in the functional study [14]. In addition, Hizawa et al [27] suggested that mononuclear cells from subjects who carried the -28G allele produced significantly greater levels of RANTES protein than cells from subjects who did not carry this allele. From these findings it seems reasonable to assume that increased concentration of RANTES in asthmatic children carrying the - AA = atopic asthma; NAA = nonatopic asthma; NC = normal controls; n = number of patients; q = minor allele frequency a Each p value was calculated with codominant (c), dominant (d), and recessive (r) models.…”

Preferential transmission and association of the −403 G → A promoter RANTES polymorphism with atopic asthma

“…However, there are population differences in the allelic frequencies, and possible contributions to allergic disease, of the two identified promoter polymorphisms as seen in the very low rates for the À28C/G polymorphism in our population in comparison to Japanese and Chinese populations. 12,17 In addition to population differences in genetic and environmental contributions to disease expression, the inheritance of asthma and atopy is likely to be complex and to be confounded by relatively small contributions from a number of different genes. It is also likely to be confounded by partial penetrance, by asymptomatic carriers who have not yet been exposed to the relevant environmental hazard and by disease phenocopies.…”

“…10 Two polymorphisms , a C to G substitution at position À28 and a G to A substitution at position À403, have been identified by sequencing a 1031 bp PCR fragment of the upstream noncoding region of the RANTES gene in a case-control HIV-1 population. 11 Three haplotypes have been found in a Japanese population with allele frequencies of 0.121 for the À28C/G and 0.329 for the À403G/A polymorphism, 12 although in Caucasian populations the distribution of these two polymorphisms has been found to be different with a lower allele frequency of 0.044 and heterozygosity of 0.089 for the À28C/G polymorphism 13 and an overall frequency of 0.161 and heterozygosity of 0.211 for the À403 G/A polymorphism. 14 The À403G/A point mutation results in a new consensus element for the GATA transcription factor family, 15 which suggests a role in the differential regulation of gene expression.…”

A polymorphism in the CCL2 chemokine gene is associated with asthma risk: a case–control and a family study in Tunisia

“…We and others reported an association between the chemokine polymorphism CCL5 (G-403A), which increases constitutive transcription activity by a factor of 8, 5,6 and asthma. [7][8][9] However, the absence of an association between asthma and the deletion of the functional allele in CCR5-D32, the principal CCL5 receptor, 10,11 suggests that other CCL5 receptors may be involved in this disease.…”