Zhao De-yu, Wen Guan-yu, Tian Man, Shi Sheng-yun, Chen Rong-hua
Department of Respiratory Medicine, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing 210008, China.
Zhonghua Er Ke Za Zhi. 2008 Feb;46(2):89-93.
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.
呼吸道合胞病毒（RSV）感染几乎所有两岁以下儿童。目前尚不清楚为什么少数感染RSV的儿童会发展为需要住院治疗的细支气管炎，而大多数儿童病情相对较轻。最近的几项研究已获得一些迹象表明基因异质性与RSV细支气管炎有关，这意味着RSV感染的临床结果可能由遗传因素决定。受激活调节的正常T细胞表达和分泌的RANTES在RSV细支气管炎的病理生理学中起关键作用。本研究的目的是探讨RANTES基因启动子-28C/G多态性与中国汉族人群RSV细支气管炎之间的遗传关联。
本研究招募了238例12个月以下因RSV导致细支气管炎而住院的患者（男186例，女52例），记录其性别、年龄、住院时间、入院时的SaO2、个人及家族过敏史。同时选取288例健康对照者（男206例，女82例），这些对照者无个人或家族过敏史且无喘息病史。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法鉴定RANTES启动子-28C/G位点的多态性。采用酶联免疫吸附测定（ELISA）法检测血清样本中的总IgE浓度。使用自动血液分析仪检测外周血嗜酸性粒细胞绝对计数。
RANTES -28C/G基因多态性分布符合Hardy-Weinberg平衡。与对照组相比，RSV细支气管炎患者RANTES -28C/G多态性的基因型和等位基因频率存在显著差异（G = 10.22，P < 0.01；χ2 = 9.708，P < 0.01）。与野生型CC相比，-28G等位基因携带者患RSV细支气管炎的风险增加2.09倍（OR = 2.09，95%CI = 1.32 - 3.30，P < 0.01）。有趣的是，在RSV细支气管炎患者中，-28G等位基因携带者的个人过敏史百分比和家族过敏史百分比均显著高于CC纯合子携带者（P < 0.05）。与野生型CC相比，-28G等位基因携带者有个人过敏史的风险增加1.85倍（OR = 1.85，95%CI = 1.01 - 3.38，P = 0.045），有家族过敏史的风险增加1.91倍（OR = 1.91，95%CI = 1.03 - 3.54，P = 0.037），且-28G等位基因携带者的外周血嗜酸性粒细胞绝对计数显著更高（P < 0.05）。
RANTES基因启动子-28C/G多态性与RSV细支气管炎易感性相关，-28G等位基因是RSV细支气管炎患者个人过敏史和家族过敏史的重要易感因素。
