RANTES启动子-28C／G基因多态性与呼吸道合胞病毒致细支气管炎易感性的关联

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

目的探讨正常T淋巴细胞表达和分泌的活性调节蛋白RANTES的启动子-28C／G基因多态性与呼吸道合胞病毒（RSV）致细支气管炎（既往称毛细支气管炎）易感的关联性。方法应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术，检测238例RSV细支气管炎患儿及288例正常对照者的RANTES-28C／G多态性，ELISA法检测血清总IgE浓度，全自动血细胞计数仪计数嗜酸性粒细胞，并搜集受检者的特应性体质史、特应性家族史及临床相关资料。结果RANTES-28C／G基因型分布在RSV细支气管炎组和对照组均符合Hardy-Weinberg平衡。与对照组比较，RANTES-28C／G基因型及等位基因频率在RSV细支气管炎组中的分布差异均有统计学意义（G=10．22，P〈0．01；X^2=9．708，P〈0．01）；与CC基因型个体相比，携带G等位基因的个体发生RSV细支气管炎的风险增加了2．09倍（OR=2．09，95％CI=1．32—3．30，P〈0．01）。在RSV细支气管炎组，携带G等位基因个体具有特应性体质和特应性家族史的风险分别比CC基因型个体增加了1．85倍（OR=1．85，95％CI=1．01—3．38，P〈0．05）和1．91倍（OR=1．91，95％CI=1．03—3．54，P〈0．05），其嗜酸性粒细胞计数亦显著升高（Z=-2．303，P〈0．05）。结论RANTES启动子-28C／G基因多态性与RSV细支气管炎易感性相关联，并且-28G等位基因与RSV细支气管炎患儿的特应性体质及特应性家族史相关联。

Objective 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. Methods 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. Results 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 ; X^2 = 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）. Conclusion 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.