A non-synonymous SNP in the NOS2 associated with septic shock in patients with sepsis in Chinese populations
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ORIGINAL INVESTIGATION
A non-synonymous SNP in the NOS2 associated with septic shock in patients with sepsis in Chinese populations Zhifu Wang • Kai Feng • Maoxing Yue • Xiaoguang Lu • Qihan Zheng • Hongxing Zhang • Yun Zhai • Peiyao Li • Lixia Yu • Mi Cai • Xiumei Zhang • Xin Kang • Weihai Shi • Xia Xia • Xi Chen • Pengbo Cao Yuanfeng Li • Huipeng Chen • Yan Ling • Yuxia Li • Fuchu He • Gangqiao Zhou
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Received: 15 August 2012 / Accepted: 20 November 2012 / Published online: 30 November 2012 Ó Springer-Verlag Berlin Heidelberg 2012
Abstract Sepsis represents a systemic inflammatory response to infection and its sequelae include severe sepsis, septic shock, multiple organ dysfunction syndrome (MODS) and death. Studies in mice and humans indicate that the inducible nitric oxide synthase (iNOS, NOS2) plays an important role in the development of sepsis and its sequelae. It was reported that several single nucleotide polymorphisms (SNPs) within NOS2 could influence the production or activity of NOS2. In this study, we assessed Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, and the State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine contributed equally to this work.
Electronic supplementary material The online version of this article (doi:10.1007/s00439-012-1253-4) contains supplementary material, which is available to authorized users. Z. Wang F. He Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China Z. Wang H. Zhang Y. Zhai P. Li L. Yu M. Cai X. Zhang X. Xia X. Chen P. Cao Y. Li F. He (&) G. Zhou (&) State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China e-mail: [email protected] G. Zhou e-mail: [email protected] K. Feng Center for Experimental Medicine and Special Medicine, 306 Hospital of PLA, Beijing, China
whether SNPs within NOS2 gene were associated with severity of sepsis in Chinese populations. A case–control study was conducted, which included 299 and 280 unrelated patients with sepsis recruited from Liaoning and Jiangsu provinces in China, respectively. Six SNPs within NOS2 were genotyped using Sequenom MassARRAY system. The associations between the SNPs and risk of sepsis complications were estimated by a binary logistic regression model adjusted for confounding factors. Functional assay was performed to assess the biological significance. The GA ? AA genotype of a non-synonymous SNP in the exon 16 of NOS2 (rs2297518: G[A) was significantly associated with increased susceptibility to septic shock compared with GG genotype in Liaoning population (OR = 3.29, 95 % CI = 1.40–7.72, P = 0.0047). This association was confirmed in the Jiangsu population X. Lu X. Kang Department of Emergency, Affiliated Zhongshan Hospital of Dalian University, Dalian, China Q. Zheng Department of E
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