To KKW, Zhou J, Song YQ, Hung IFN, Ip WCT, Cheng ZS, Chan ASF, Kao RYT, Wu AKL, Chau S, Luk WK, Ip MSM, Chan KH, and Yuen KY
Background: Surfactant proteins play a key role in alveolar stability. We examined whether single nucleotide polymorphisms (SNPs) related to the surfactant protein genes are associated with severe influenza., Methods: In the first cohort, 12 SNPs related to surfactant protein genes were compared between Chinese patients with severe and mild pandemic 2009 influenza A(H1N1) (A[H1N1]pdm09) infection who were matched for age, sex, and underlying risk conditions. The SNP rs1130866, which was significantly different between the two groups, was further genotyped in a second cohort of patients. Multivariate analysis was performed to control for confounding factors. The genotype frequencies were also compared with those of the general Han Chinese population., Results: This study consisted of 380 patients with A(H1N1)pdm09 infection. In the first cohort of 84 patients, the C allele of rs1130866, an SNP in the surfactant protein B gene (SFTPB), was significantly associated with severe disease (OR = 3.37, P = .0048), although the P value was .057 after Bonferroni correction. In the second cohort of 296 patients, the C/C genotype was confirmed in the univariate analysis to be associated with severe disease. Multivariate analysis of the second cohort showed that genotype C/C was an independent risk factor for severe A(H1N1)pdm09 infection (second cohort: OR = 2.087, P = .023). Compared to the general Han Chinese population, the C/C genotype was overrepresented in patients with severe A(H1N1)pdm09 infection (OR = 3.232, P = .00000056)., Conclusions: SFTPB polymorphism is associated with severe influenza. The role of SFTPB in influenza warrants further studies.