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.

Artichoke, Cynarin and Cyanidin Downregulate the Expression of Inducible Nitric Oxide Synthase in Human Coronary Smooth Muscle Cells

“…iNOS mutant mice have a blunted hypotensive response to sepsis [14]. Recently, a non-synonymous SNP in the iNOS gene has been shown to be associated with increased susceptibility to septic shock in Chinese populations [15].…”

Inducible Nitric Oxide Synthase Polymorphisms and Nitric Oxide Levels in Individuals with Chronic Periodontitis

“…As suggested by Wang et al, 2013 [28] besides the SNPs investigated here, we cannot exclude the possibility of the presence of other functional polymorphisms in linkage disequilibrium (LD) with an investigated SNP being responsible for the genotype-dependent differences in iNOS activity. Further studies are needed to identify polymorphisms in this region and clarify which polymorphism(s) may possess the functional consequence(s) for the genotype-dependent differences in iNOS activity (e.g., NO levels), and provide mechanistic plausibility for the observed association between NOS2 and susceptibility to CP.…”

“…Both −1026(A>C) and +2087(A>G) single nucleotide polymorphisms (SNPs) in the NOS2 gene are potentially functional [12,18,23,28,29] and clinically relevant, as they are associated with hypertensive disorders [29,30,31,32], migraine with aura [26], and malignant neoplasias [33,34]. …”

Endothelial Nitric Oxide Synthase G894T Polymorphism Associates with Disease Severity in Puumala Hantavirus Infection

“…Previous studies have indicated that iNOS plays an important role in the origin of hypotension in septic shock. The A-allele carriage has been associated with increased susceptibility to septic shock [ 29 ]. Our finding indicated that the rare A-allele carriers ( i .…”