More severe clinical course of cardiovascular dysfunction in intensive care unit patients with the 894TT eNOS genotype

Abstract

ABSTRACT. The endothelial nitric oxide synthase (eNOS) plays an important homeostatic role in the cardiovascular system (CVS) by maintaining appropriate blood pressure through production of nitric oxide. The 894TT genotype of 894G>T (Glu298Asp, rs1799983), a polymorphic variant of eNOS, has been associated with several vascular diseases. On the basis of this strong relationship, we monitored daily 585 critically ill adult patients according to their degree of CVS dysfunction and investigated their disease progression by the 894G>T genotype. To obtain information of the general population, we obtained the 894G>T eNOS and CVS dysfunction in critically ill patients genotypic and allelic frequencies in a random group of 149 healthy subjects. The patients were genotyped for the eNOS 894G>T polymorphism and daily evaluated according to their degree of CVS dysfunction through the Cardiovascular Sequential Organ Failure Assessment (SOFA) score. The mean value of the global CVS dysfunction score was significantly higher in 894TT patients (1.35 ± 0.57) than in non-894TT patients (1.23 ± 0.37; P = 0.035). This score remained significantly higher in 894TT patients, even in different patient clusters (all patients, septic, and nonseptic patients) during the 1st week at the intensive care unit (1.86 ± 0.8 versus 1.63 ± 0.62, P = 0.005; 2.32 ± 0.10 versus 2.06 ± 0.08, P = 0.009; 0.84 ± 0.09 versus 0.64 ± 0.08, P = 0.027; respectively). This result shows that the mean values of the cardiovascular SOFA score were higher in 894TT patients in all subgroups. The present study provides evidence that the 894TT eNOS genotype is associated with a higher degree of CVS dysfunction in critically ill patients.

Variants in TNF and NOS3 (eNOS) genes associated with sepsis in adult patients

“…Aspartate at position 298 was shown to be subjected to selective proteolytic cleavage in endothelial cells and vascular tissues that may be responsible for the T allele being a risk factor for vascular disease 24 . Indeed, Fraga et al 45 . found that the degree of cardiovascular dysfunction was higher in 894TT patients with sepsis, indicating that the effect of this genotype is an independent factor of cardiovascular dysfunction.…”

Nitric Oxide Synthase 3 Gene Variants and Colorectal Cancer: a Meta-Analysis

“…In addition, a meta-analysis was conducted by Yao et al in 2010, declaring that rs1799983 was associated with reduced breast cancer risk (Yao et al, 2010). Furthermore, rs1799983 was also said to be related to many other diseases such as recurrent miscarriage (Luo et al, 2013) and cardiovascular diseases (Fraga et al, 2013). Considering the important role of NOS3 gene in the cancers and vasculopathy, we suggested that as one of the promising SNP rs1799983 might be the key polymorphism of NOS3 gene influencing CRC risk which might be useful in the genetic target therapy.…”

Η Συσχέτιση Των Πολυμορφισμών G894T Και T786C Του Γονιδίου Της Ενδοθηλιακής Συνθετάσης Του Νιτρικού Οξειδίου Με Τη Λειτουργικότητα Των Αγγείων Και Τη Φλεγμονή Σε Ασθενείς Με Σακχαρώδη Διαβήτη Και Διαβητικό Πόδι

“…Καταγράφηκε στατιστικά σημαντική μέση καρδιοαγγειακή τιμή βαθμολόγησης στην ομάδα των ασθενών με τον 894TT γονότυπο, η οποία και παρέμεινε στατιστικά σημαντική ανεξαρτήτως της υποομάδας στην οποία ανήκαν οι εκάστοτε ασθενείς (Πίνακας 3). Ως εκ τούτου, ο 894TT γονότυπος σχετίζεται με αυξημένο βαθμό καρδιοαγγειακής δυσλειτουργίας σε βαρέως πάσχοντες ασθενείς [295].…”