Department of Pediatrics, Harvard Medical School, Massachusetts General Hospital for Children, Boston, MA 02114, USA.
J Pediatr. 2010 Mar;156(3):409-14. doi: 10.1016/j.jpeds.2009.09.043. Epub 2009 Nov 14.
To examine whether genetic variations within the surfactant protein A2 (SP-A2) gene are associated with respiratory syncytial virus (RSV) disease severity in infected children.
Naturally infected children aged < or =24 months were prospectively enrolled in 3 RSV seasons. SP-A2 genotyping was performed. Independent clinical predictors of disease severity were analyzed. The association of SP-A2 genetic diversity and disease severity was tested by using multivariate logistic regression models and 4 levels of disease gradation as outcome measures.
Homozygosity of the 1A(0) allele was protective against hospitalization (odds ratio [OR] = 0.15, P = .0010). This remained significant in African American patients (OR = 0.24, P = .042) and Caucasian patients (OR = 0.05, P = .021) after adjustment for other co-variates. Hospitalized children with the 1A(2) allele demonstrated significant protection from severe disease with univariate analyses, but only a trend for protection with multivariate analyses. Patients homozygous or heterozygous for an asparagine at amino acid position 9 were twice or more likely to need intensive care unit admission (OR = 2.15, P = .022), require intubation (OR = 3.04, P = .005), and have a hospitalization lasting > or =4 days (OR = 1.89, P = .02) compared with children homozygous for a threonine at this position.
SP-A2 polymorphisms are associated with the severity of RSV infection in infants.
研究表面活性蛋白 A2(SP-A2)基因内的遗传变异是否与呼吸道合胞病毒(RSV)感染患儿的疾病严重程度相关。
3 个 RSV 流行季前瞻性纳入年龄≤24 个月的自然感染患儿,进行 SP-A2 基因分型。分析独立的临床疾病严重程度预测因子。采用多元逻辑回归模型和 4 级疾病分级作为结局指标,检验 SP-A2 遗传多样性与疾病严重程度的相关性。
1A(0)等位基因纯合子对住院治疗有保护作用(比值比[OR] = 0.15,P =.0010)。校正其他协变量后,该结果在非裔美国患者(OR = 0.24,P =.042)和白种患者(OR = 0.05,P =.021)中仍然具有统计学意义。单变量分析显示,携带 1A(2)等位基因的住院患儿发生严重疾病的风险显著降低,但多变量分析仅显示出保护趋势。与该位置为苏氨酸的患儿相比,天冬酰胺位于该位置的患儿纯合或杂合时,更有可能需要入住重症监护病房(OR = 2.15,P =.022)、需要插管(OR = 3.04,P =.005),以及住院时间超过 4 天(OR = 1.89,P =.02)。
SP-A2 多态性与 RSV 感染婴儿的严重程度相关。