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: 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
• Journal: Human genetics (Hum Genet) Vol. 132 Issue 3 Pg. 337-46 (Mar 2013) ISSN: 1432-1203 [Electronic] Germany
• PMID: 23192595 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NOS2 protein, human
• Nitric Oxide Synthase Type II

Topics

• APACHE
• Adult
• Aged
• Asian People (statistics & numerical data)
• Case-Control Studies
• China (epidemiology)
• Female
• Genetic Predisposition to Disease
• Genotype
• Humans
• Male
• Middle Aged
• Nitric Oxide Synthase Type II (genetics)
• Phenotype
• Polymerase Chain Reaction
• Polymorphism, Restriction Fragment Length
• Polymorphism, Single Nucleotide
• Risk Factors
• Sepsis (enzymology, epidemiology, genetics)
• Severity of Illness Index
• Shock, Septic (enzymology, epidemiology, genetics)