The Association Of The RANTES Gene Promoter-403G/A And -28C/G Polymorphisms With Respiratory Syncytial Virus Bronchiolitis

Objective: To explore the genetic association between the regulated on activation, normal T cell expressed and secreted(RANTES) gene promoter -403G/A and -28C/G polymorphisms and respiratory syncytial virus(RSV) bronchiolitis in Chinese Han nationality population.Methods: Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) was used to identify the polymorphisms at position -403G/A and -28C/G of the RANTES promoter in 238 patients with RSV bronchiolitis and 288 healthy controls. The total IgE concentrations in serum samples were measured by Enzyme-linked immunosorbent assay(ELISA). The absolute peripheral blood eosinophil counts were measured by Automated Hematology Analyzer. Clinical data such as the personal history of atopy(PHA) and the family history of atopy(FHA) were also collected.Results:(1) The distribution of RANTES -403G/A and -28C/G gene polymorphisms were in accordance with Hardy-Weinberg equilibrium.(2) Compared to control subjects, no significant difference was demonstrated for genotypes and allele frequencies of the RANTES -403G/A polymorphism in RSV bronchiolitis(P＞0.05). But the total IgE levels indicated significant difference among the three genetypes in RSV bronchiolitis(P＜0.05).(3) Compared to control subjects, significant difference was demonstrated for genotypes and allele frequencies of the RANTES -28C/G polymorphism in RSV bronchiolitis(P＜0.01). Compared to the wild type CC, the -28G allele carriers(CG+GG) demonstrated a 2.09-fold increased risk of RSV bronchiolitis(OR=2.09, 95%CI=1.32-3.30, P=0.001).(4) For RANTES -403G/A, both the percentage of PHA and the percentage of FHA showed significant difference among the three genetypes of -403G/A in RSV bronchiolitis(P＜0.05). Compared to the wild type GG, the -403A allele carriers demonstrated a 2.57-fold increased risk of PHA(OR=2.57, 95%CI=1.44-4.60, P=0.001) and a 2.17-fold increased risk of FHA(OR=2.17, 95%CI=1.17-4.01, P=0.013). Interestingly, compared to the wild type GG, the AA homozygotes carriers demonstrated a 2.64-fold increased risk of PHA(OR=2.64, 95%CI=1.13-6.16, P=0.023) and a 2.68-fold increased risk of FHA (OR=2.68, 95%CI=1.12-6.42, P=0.024). For RANTES -28C/G, both the percentage of PHA and the percentage of FHA for the -28G allele carriers were significantly higher(P＜0.05) than that for those CC homozygotes carriers in RSV bronchiolitis. Compared to the wild type CC, the -28G allele carriers demonstrated a 1.85-fold increased risk of PHA(OR=1.85, 95%CI=1.01-3.38, P=0.045) and a 1.91-fold increased risk of FHA(OR=1.91, 95%CI=1.03-3.54, P=0.037), and the absolute peripheral blood eosinophil counts for the -28G allele carriers were significantly higher(P＜0.05).(5) In addition, strong linkage disequilibrium(LD) between -403G/A and -28C/G was observed in our study population and only three haplotypes:Ⅰ(GC),Ⅱ(AC) andⅢ(AG) were identified. The haplotypeⅢwas more prevalent in RSV bronchiolitis as compared to the control subjects. Similar results were observed in PHA and FHA as compared to non PHA and non FHA. The distribution of six haplotype pairs was significant difference in RSV bronchiolitis and control subjects, so in PHA and non PHA. Furthermore, The haplotype pairsⅠ*ⅢandⅡ*Ⅲwere more prevalent in RSV bronchiolitis as compared to the control subjects (P＜0.05). Compared to other haplotype pairs, subjects earring the haplotype pairsⅠ*Ⅲdemonstrated a 1.74-fold increased risk of RSV bronchiolitis(OR=1.74, 95%CI=1.01-2.98, P=0.043), and subjects carring the haplotype pairsⅡ*Ⅲdemonstrated a 2.69-fold increased risk of RSV bronchiolitis(OR=2.69, 95%CI=1.14-6.35, P=0.019).Conclusion: (1) The RANTES gene -403G/A polymorphism maybe not associate with the susceptibility of RSV bronchiolitis in Chinese Han nationality population. However, the -403G/A perhaps contribute to the susceptibility of RSV bronchiolitis with -28C/G polymorphism in the context of haplotype.(2) The RANTES gene -28C/G polymorphism is associate with the susceptibility of RSV bronchiolitis, and the -28G allele is an important predisposing factor for RSV bronchiolitis.(3) The RANTES gene -403G/A and -28C/G polymorphisms and the haplotypes derived from them are correlate with the risk of patients with RSV bronchiolitis carring PHA and FHA.