It has been demonstrated that two functional polymorphisms in the proximal promoter region of the RANTES gene (-28C to G and -403G to A) increase transcriptional activity of RANTES gene and RANTES expression in the human body.[12
] Increased production of RANTES would be expected to increase the level of inflammatory cell recruitment, as it is one of the major chemo-attractant proteins for eosinophil[9
] and other cells into asthmatic airways after allergen challenge.[17
] It is therefore quite likely that these polymorphisms are possible loci involved in asthma susceptibility.
Results obtained from this study showed no significant association between the RANTES -403A allele or the -28G allele and asthma in the Lebanese population. According to these results, these polymorphisms in the promoter region of the RANTES gene do not influence significantly the development of asthma.
These results were consistent with reports from Korean,[29
] and African American[32
] populations where RANTES promoter polymorphism did not have a significant effect on the susceptibility to asthma.
On the contrary, some other studies suggested a positive association between RANTES polymorphisms and asthma susceptibility, or with different types of bronchial asthma. A study by Lachheb et al
. on Tunisian children[33
] suggested an association between alleles level of -28C/G and -403G/A promoter polymorphism and asthma. In addition, a study on Northern European Caucasians population[34
] found that the -403A allele was associated with an increased susceptibility to both asthma and atopy.
In view of the plausible role of the -403G/A polymorphism in promoting allergic responses and its high allelic frequency in Caucasian populations, Abdulhadi et al
] sought to confirm or refute the previous reported case–control study[32
] using a family-based association tests (FBATs) and generation-specific case-control analyses. The -403G/A was transmitted with atopy and atopic asthma, although its contribution appears to relate more to atopy than asthma and BHR.
Several studies of the RANTES genotypes in the Asian populations have supported this association. In a Chinese cohort by Wang et al
] the prevalence of the -28G allele was significantly different between asthmatic patients and controls (19.5% vs. 10.6%). Also, the levels of plasma RANTES and peripheral eosinophils were significantly different among the three genotypes but not the total levels of plasma IgE.
Our results were consistent with previous report in Korean children,[29
] where no significant differences in clinical characteristics according to the genotypes of RANTES -403G/A polymorphism were observed. Also, in the Hungarian study,[30
] no clinical or laboratory characteristics were associated with a given RANTES genotype.
RANTES genotype was shown to be associated with increasing severity of airway obstruction in a previous study by Fryer et al
] However, a meta-analysis comprising several studies[21
] was carried out by Zhang et al
] and confirmed the absence of significant associations of the -403G/A and -28C/G polymorphisms with asthma.
According to our results, these polymorphisms in the promoter region of the RANTES gene do not influence significantly the development of asthma, atopy, or the eosinophil count. It can be assumed that these more inducible RANTES genes do not have a detectable effect on the investigated parameters or that, more simply, in those cells (e.g., airway epithelial cells) that participate in the pathomechanism of these diseases, other cis-regulating elements are responsible for the expression of RANTES.
The main weakness of this study relates to the sample size of both cases and controls. There has not been any report on allele frequencies of RANTES G-403A and C-28G in the Lebanese population at the time of this study, and this made sample size estimation difficult. This study may thus be underpowered on detecting any association between G-403A and rare outcomes. A further study with a larger population size is thus needed.
Our results showed that RANTES gene promoter polymorphisms are not associated with asthma susceptibility in the Lebanese population.