Effect of angiotensin-converting enzyme tag single nucleotide polymorphisms on the outcome of patients with traumatic brain injury. Issue 10 (October 2015)

• Record Type: Journal Article
• Authors: Dardiotis, Efthimios; Paterakis, Konstantinos; Siokas, Vasileios; Tsivgoulis, Georgios; Dardioti, Maria; Grigoriadis, Savas; Simeonidou, Constantina; Komnos, Apostolos; Kapsalaki, Eftychia; Fountas, Kostas; Hadjigeorgiou, Georgios M.
• Is Part Of: Pharmaocogenetics and genomics. Volume 25:Issue 10(2015:Oct.)
• Publication Date: 2015-10
• Subjects: Pharmacogenetics -- Periodicals; Pharmacogenomics -- Periodicals; Genetic toxicology -- Periodicals; Biomedical genetics -- Periodicals; 615.7
• DOI: 10.1097/FPC.0000000000000161
• Languages: English
• ISSNs: 1744-6872

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Background</title> <p>Genetic variants appear to influence, at least to some degree, the extent of brain injury and the clinical outcome of patients who have sustained a traumatic brain injury (TBI). Angiotensin-converting enzyme (ACE) is a zinc metallopeptidase that is implicated in the regulation of blood pressure and cerebral circulation. <italic>ACE</italic> gene polymorphisms were found to regulate serum ACE enzyme activity.</p> </sec> <sec> <title>Objective</title> <p>The present study aimed to investigate possible influence of <italic>ACE</italic> gene region variants on patients' outcome after TBI.</p> </sec> <sec> <title>Patients and methods</title> <p>In total, 363 TBI patients prospectively enrolled in the study were genotyped for five tag single nucleotide polymorphisms (SNPs) across the <italic>ACE</italic> gene. Using logistic regression analyses, tag SNPs and their constructed haplotypes were tested for associations with 6-month Glasgow Outcome Scale scores, after adjustment for age, sex, Glasgow Coma Scale scores at admission, and the presence of a hemorrhagic event in the initial computed tomography scan.</p> </sec> <sec> <title>Results</title> <p>Significant effects on TBI outcome were found for three neighboring tag SNPs in the codominant (genotypic) model of inheritance [rs4461142: odds ratio (OR) 0.26, 95% confidence interval (CI) 0.12–0.57, <italic>P</italic>=0.0001; rs7221780: OR 2.67, 95% CI 1.25–5.72, <italic>P</italic>=0.0003; and rs8066276: OR 3.82, 95% CI 1.80–8.13, <italic>P</italic>=0.0002; for the heterozygous variants compared with the common alleles]. None of the constructed common tag SNPs haplotypes was associated with TBI outcome.</p> </sec> <sec> <title>Conclusion</title> <p>The present study provides evidence of the possible influence of genetic variations in a specific region of the <italic>ACE</italic> gene on the outcome of TBI patients. This association may have pharmacogenetic implications in identifying those TBI patients who may benefit from ACE inhibition.</p> </sec> </abstract>