Association of RANTES gene promoter -28C/G polymorphism with respiratory syncytial virus bronchiolitis

Abstract

Respiratory syncytial virus (RSV) infects nearly all children under two years of age. It is poorly understood why a few children who were infected with RSV develop bronchiolitis that require hospital admission while most have a relatively minor illness. Several recent studies have obtained some indications for the involvement of genetic heterogeneity in RSV bronchiolitis, implying that the clinical outcome of RSV infection perhaps is determined by genetic factors. Regulated on activation, normal T cell expressed and secreted RANTES plays a key role in the pathophysiology of RSV bronchiolitis. The purpose of this study was to explore the genetic association between the RANTES gene promoter -28C/G polymorphism and RSV bronchiolitis in Chinese Han ethnic group population. The study recruited 238 hospitalized patients (186 male and 52 female) under 12 months of age, with a clinical diagnosis of bronchiolitis due to RSV, the sex, age, hospital stay, SaO2 at the time of admission, personal and family history of atopy were recorded. The 288 healthy control subjects (206 male and 82 female), who had no evidence of personal or familial history of atopy and no history of wheezing, were chosen at the same time. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to identify the polymorphism at position -28C/G of the RANTES promoter. The total IgE concentrations in serum samples were measured by enzyme-linked immunosorbent assay (ELISA). The absolute peripheral blood eosinophil counts were measured by using an automated hematology analyzer. The distribution of RANTES -28C/G gene polymorphism was in accordance with Hardy-Weinberg equilibrium. Compared to control subjects, significant difference was demonstrated for genotypes and allele frequencies of the RANTES -28C/G polymorphism in patients with RSV bronchiolitis (G = 10.22, P < 0.01; chi2 = 9.708, P < 0.01). Compared with the wild type CC, the -28G allele carriers demonstrated a 2.09-fold increased risk of RSV bronchiolitis (OR = 2.09, 95% CI = 1.32 - 3.30, P < 0.01). Interestingly, both the percentage of personal history of atopy and the percentage of family history of atopy for the -28G allele carriers were significantly higher (P < 0.05) than that for those CC homozygotes carriers in RSV bronchiolitis. Compared with the wild type CC, the -28G allele carriers demonstrated a 1.85-fold increased risk of the personal history of atopy (OR = 1.85, 95% CI = 1.01 - 3.38, P = 0.045) and a 1.91-fold increased risk of the family history of atopy (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). The RANTES gene promoter -28C/G polymorphism is associated with the susceptibility to RSV bronchiolitis, and the -28G allele is an important predisposing factor for the personal history of atopy and the family history of atopy in RSV bronchiolitis.