Kelvin K W To1, Jie Zhou2, You-Qiang Song3, Ivan F N Hung4, Whitney C T Ip5, Zhong-Shan Cheng5, Andy S F Chan5, Richard Y T Kao6, Alan K L Wu7, Sandy Chau8, Wei-Kwang Luk9, Mary S M Ip10, Kwok-Hung Chan11, Kwok-Yung Yuen12. 1. State Key Laboratory for Emerging Infectious Diseases; Carol Yu Centre for Infection; Research Centre of Infection and Immunology; Department of Microbiology. 2. Research Centre of Infection and Immunology; Department of Microbiology. 3. Department of Biochemistry. 4. Carol Yu Centre for Infection; Research Centre of Infection and Immunology; Department of Medicine, The University of Hong Kong, Pokfulam. 5. Department of Microbiology. 6. State Key Laboratory for Emerging Infectious Diseases; Research Centre of Infection and Immunology; Department of Microbiology. 7. Department of Pathology, Pamela Youde Nethersole Eastern Hospital, Hong Kong Special Administrative Region. 8. Department of Pathology, United Christian Hospital, Hong Kong Special Administrative Region. 9. Department of Pathology, Tseung Kwan O Hospital, Hong Kong Special Administrative Region, China. 10. Department of Medicine, The University of Hong Kong, Pokfulam. 11. Carol Yu Centre for Infection; State Key Laboratory for Emerging Infectious Diseases; Research Centre of Infection and Immunology; Department of Microbiology. 12. Department of Microbiology; Research Centre of Infection and Immunology; Carol Yu Centre for Infection; State Key Laboratory for Emerging Infectious Diseases. Electronic address: kyyuen@hku.hk.
Abstract
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.
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.
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