Polymorphism of Nitric Oxide Synthase 1 Affects the Clinical Phenotypes of Ischemic Stroke in Korean Population

Abstract

ObjectiveTo investigate whether four single nucleotide polymorphisms (SNPs) rs2293054 [Ile734Ile], rs1047735 [His902His], rs2293044 [Val1353Val], rs2682826 (3'UTR) of nitric oxide synthase 1 (NOS1) are associated with the development and clinical phenotypes of ischemic stroke.MethodsWe enrolled 120 ischemic stroke patients and 314 control subjects. Ischemic stroke patients were divided into subgroups according to the scores of the National Institutes of Health Stroke Survey (NIHSS, <6 and ≥6) and Modified Barthel Index (MBI, <60 and ≥60). SNPStats, SNPAnalyzer, and HelixTree programs were used to calculate odds ratios (ORs), 95% confidence intervals (CIs), and p-values. Multiple logistic regression models were performed to analyze genetic data.ResultsNo SNPs of the NOS1 gene were found to be associated with ischemic stroke. However, in an analysis of clinical phenotypes, we found that rs2293054 was associated with the NIHSS scores of ischemic stroke patients in codominant (p=0.019), dominant (p=0.007), overdominant (p=0.033), and log-additive (p=0.0048) models. Also, rs2682826 revealed a significant association in the recessive model (p=0.034). In allele frequency analysis, we also found that the T alleles of rs2293054 were associated with lower NIHSS scores (p=0.007). Respectively, rs2293054 had a significant association in the MBI scores of ischemic stroke in codominant (p=0.038), dominant (p=0.031), overdominant (p=0.045), and log-additive (p=0.04) models.ConclusionThese results suggest that NOS1 may be related to the clinical phenotypes of ischemic stroke in Korean population.

The rs2682826 Polymorphism of the NOS1 Gene Is Associated with the Degree of Disability of Erectile Dysfunction

“…NO is the main inhibitor of the esophageal myenteric plexus, meaning that it progressively delays muscle contraction in the esophagus, and in this context, carriers of the variant genotype of this polymorphism may have a lower function of the gene. In addition, other studies contribute to this argument, in which the variant allele of rs2682826 is associated with a lower function of the gene [ 29 , 45 , 46 , 47 ].…”

Association of NOS1 gene polymorphisms with cerebral palsy in a Han Chinese population: a case-control study

“…Associations of NOS1 with various diseases have been reported, such as schizophrenia, Parkinson’s disease, suicide, achalasia, multiple sclerosis, ischemic stroke, and hypertension. In previous studies found that the T allele of rs2293054 was associated with lower NIHSS scores and with NIHSS scores of ischemic stroke patients in different inherited model [ 43 ]. But in our result, rs2293054 showed no relationship with CP.…”

“…The synonymous SNP (rs2682826) located in the 3’-UTR of exon 29 of the NOS1 gene was selected as the tag SNP for one of the most frequent haplotypes. The SNP rs2682826 is located close to several miRNA-binding sites in the gene’s 3′-UTR, and it likely affects the stability and translational efficiency of mRNA [ 43 – 45 ]. Some polymorphisms in NOS1 gene can directly affect the expression of mRNA, which change the levels of NO [ 46 , 47 ].…”

Endothelial nitric oxide synthase gene glu298asp polymorphism in preterm neonates with respiratory distress syndrome

“…10 Also, NO modulates immuneregulation, surfactant maturation or secretion. 11 In this study, we found statistical increases in TT, GT+TT genotype and T allele among RDS compared to controls.…”

“…1 Congenital anomalies, inherited metabolic disorders and sepsis were excluded. Neonates were subjected to history taking, general and local examinations; APGAR score [normal (8)(9)(10), mild (6)(7)(8), moderate (3)(4)(5), severe (0-2)]. Complete blood count and arterial blood gas were performed (ABG for RDS neonates only).…”