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Original Research: Chest Infections |

Surfactant Protein B Gene Polymorphism Is Associated With Severe InfluenzaSurfactant Protein B and Influenza

Kelvin K. W. To, MD; Jie Zhou, PhD; You-Qiang Song, PhD; Ivan F. N. Hung, MD; Whitney C. T. Ip, BSc; Zhong-Shan Cheng, MPhil; Andy S. F. Chan, BSc; Richard Y. T. Kao, PhD; Alan K. L. Wu, MD; Sandy Chau, MD; Wei-Kwang Luk, MD; Mary S. M. Ip, MD, FCCP; Kwok-Hung Chan, PhD; Kwok-Yung Yuen, PhD
Author and Funding Information

From the State Key Laboratory for Emerging Infectious Diseases (Drs To, Kao, K.-H. Chan, and Yuen), Carol Yu Centre for Infection (Drs To, Hung, K.-H. Chan, and Yuen), Research Centre of Infection and Immunology (Drs To, Zhou, Hung, Kao, K-H. Chan, and Yuen), Department of Microbiology (Drs To, Zhou, Kao, K.-H. Chan, and Yuen; Ms W. C. T. Ip; and Messrs Cheng and A. S. F. Chan), Department of Biochemistry (Dr Song), and Department of Medicine (Drs Hung and M. S. M. Ip), The University of Hong Kong, Pokfulam; Department of Pathology (Dr Wu), Pamela Youde Nethersole Eastern Hospital, Hong Kong Special Administrative Region; Department of Pathology (Dr Chau), United Christian Hospital, Hong Kong Special Administrative Region; and the Department of Pathology (Dr Luk), Tseung Kwan O Hospital, Hong Kong Special Administrative Region, China.

Correspondence to: Kwok-Yung Yuen, PhD, Carol Yu Centre for Infection and Division of Infectious Diseases, Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Rd, Pokfulam, Hong Kong Special Administrative Region, China; e-mail: kyyuen@hku.hk


For editorial comment see page 1186

Funding/Support: This study is supported by the Health and Medical Research Fund of the Food and Health Bureau of the Hong Kong SAR Government [Project No. 13120842] and the Providence Foundation Limited, in memory of the late Dr Lui Hac Minh.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;145(6):1237-1243. doi:10.1378/chest.13-1651
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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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