title: A non-synonymous SNP in the NOS2 associated with septic shock in patients with sepsis in Chinese populations.
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 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.affiliation: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Zhifu
authors.initials: Z
authors.lastname: Wang
authors.forename: Kai
authors.initials: K
authors.lastname: Feng
authors.forename: Maoxing
authors.initials: M
authors.lastname: Yue
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Lu
authors.forename: Qihan
authors.initials: Q
authors.lastname: Zheng
authors.forename: Hongxing
authors.initials: H
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhai
authors.forename: Peiyao
authors.initials: P
authors.lastname: Li
authors.forename: Lixia
authors.initials: L
authors.lastname: Yu
authors.forename: Mi
authors.initials: M
authors.lastname: Cai
authors.forename: Xiumei
authors.initials: X
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Kang
authors.forename: Weihai
authors.initials: W
authors.lastname: Shi
authors.forename: Xia
authors.initials: X
authors.lastname: Xia
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Pengbo
authors.initials: P
authors.lastname: Cao
authors.forename: Yuanfeng
authors.initials: Y
authors.lastname: Li
authors.forename: Huipeng
authors.initials: H
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Ling
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Li
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
authors.forename: Gangqiao
authors.initials: G
authors.lastname: Zhou
mesh_terms: D018806:APACHE; D000328:Adult; D000368:Aged; D044466:Asian People / Q000706:statistics & numerical data*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D018805:Sepsis / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*
chemical_list: C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II