Lahti Meri, Lofgren Johan, Marttila Riita, Renko Marjo, Klaavuniemi Tuula, Haataja Ritva, Ramet Mika, Hallman Mikko
Department of Pediatrics and Biocenter Oulu, University of Oulu, PO Box 5000, FIN-90014 Oulu, Finland.
Pediatr Res. 2002 Jun;51(6):696-9. doi: 10.1203/00006450-200206000-00006.
Respiratory syncytial virus (RSV) is the major respiratory tract pathogen in infancy. Host-related differences in susceptibility to severe RSV infection suggest that genetic factors may play a role. In this study, a candidate-gene approach was used to study whether the surfactant protein D (SP-D) gene polymorphism associates with severe RSV infection. DNA samples from 84 infants hospitalized for the treatment of RSV bronchiolitis and 93 healthy controls were analyzed. The controls were matched with the cases on the basis of sex, hospital district, date of birth (+/-2 wk) and gestational age at birth (+/-2 wk). Three biallelic SP-D gene polymorphisms were genotyped. Significant differences were observed in the SP-D allele frequencies for amino acid 11 between the RSV infants and their matched controls. The frequency of the allele coding for Met 11 (p = 0.033) was increased in the severe RSV group. The frequency of the homozygous genotype Met/Met for amino acid 11 was increased in the RSV group relative to the controls, whereas the heterozygous genotype tended to be less frequent among the RSV cases than in the matched controls. Conditional logistic regression analysis was used to study whether the confounders, i.e. smoking and number of children in the family, influence the association between the homozygous SP-D genotype for methionine 11 and the risk of RSV bronchiolitis. The results further confirmed this association (p = 0.028). To our knowledge, the present report provides the first evidence of a specific gene associated with susceptibility to severe RSV infection.
呼吸道合胞病毒（RSV）是婴儿期主要的呼吸道病原体。宿主对严重RSV感染易感性的差异表明遗传因素可能起作用。在本研究中，采用候选基因方法研究表面活性蛋白D（SP-D）基因多态性是否与严重RSV感染相关。分析了84例因RSV细支气管炎住院治疗的婴儿和93例健康对照的DNA样本。对照在性别、院区、出生日期（±2周）和出生时胎龄（±2周）方面与病例匹配。对三个双等位基因SP-D基因多态性进行了基因分型。在RSV感染婴儿与其匹配对照之间，观察到第11位氨基酸的SP-D等位基因频率存在显著差异。严重RSV组中编码第11位Met的等位基因频率增加（p = 0.033）。相对于对照，RSV组中第11位氨基酸的纯合基因型Met/Met频率增加，而杂合基因型在RSV病例中往往比匹配对照中更少见。采用条件逻辑回归分析研究混杂因素，即吸烟和家庭子女数量，是否影响第11位蛋氨酸的SP-D纯合基因型与RSV细支气管炎风险之间的关联。结果进一步证实了这种关联（p = 0.028）。据我们所知，本报告首次提供了与严重RSV感染易感性相关的特定基因的证据。
