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A non-synonymous SNP in the NOS2 associated with septic shock in patients with sepsis in Chinese populations.
MedLine Citation:
PMID:  23192595     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 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 (OR = 3.49, 95 % CI = 1.57-7.79, P = 0.0019). Furthermore, the functional assay performed in the immortalized lymphocyte cell lines indicated that the at-risk GA genotype had a tendency of higher NOS2 activity than the GG genotype (P = 0.32). Our findings suggest that the NOS2 rs2297518 may play a role in mediating the susceptibility to septic shock in patients with sepsis in Chinese populations.
Authors:
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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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-30
Journal Detail:
Title:  Human genetics     Volume:  -     ISSN:  1432-1203     ISO Abbreviation:  Hum. Genet.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7613873     Medline TA:  Hum Genet     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
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