Transmission of surfactant protein variants and haplotypes in children hospitalized with respiratory syncytial virus

Severity of lung injury with respiratory syncytial virus (RSV) infection is variable and may be related to genetic variations. This preliminary report describes a prospective, family-based association study of children hospitalized secondary to RSV, aimed to determine whether intragenic and other haplotypes of surfactant proteins (SP)-A and SP-D are transmitted disproportionately from parents to offspring with RSV disease. Genomic DNA was genotyped for several SP-A and SP-D single nucleotide polymorphisms (SNPs). Transmission disequilibrium test analysis was used to determine transmission of variants and haplotypes from parents to affected offspring. Three hundred seventy-five individuals were studied, including 148 children with active RSV disease and one or both parents. The SP-A2 intragenic haplotype 1A2 was found to be protective (p = 0.013). The SP-D SNP DA160-A may possibly be an at-risk marker (p = 0.0058). Additional two-and three-marker haplotypes were associated with severe RSV disease, with two being protective (DA11-T/DA160-G and DA160-G/ SP-A2 1A0/SP-A1 6A²). We conclude that there may be associations between SP-A and SP-D and RSV disease. Further study is required to determine whether these variants can be used to target a high-risk patient population in clinical trials aimed at reducing either the symptoms of acute infection or long-term pulmonary sequelae.