Effect of angiotensin-converting enzyme tag single nucleotide polymorphisms on the outcome of patients with traumatic brain injury

Efthimios Dardiotis, Konstantinos Paterakis, Vasileios Siokas, Georgios Tsivgoulis, Maria Dardioti, Savas Grigoriadis, Constantina Simeonidou, Apostolos Komnos, Eftychia Kapsalaki, Kostas Fountas, Georgios M. Hadjigeorgiou

Research output: Contribution to journalArticle

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Abstract

Background 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. ACE gene polymorphisms were found to regulate serum ACE enzyme activity. Objective The present study aimed to investigate possible influence of ACE gene region variants on patients' outcome after TBI. Patients and methods In total, 363 TBI patients prospectively enrolled in the study were genotyped for five tag single nucleotide polymorphisms (SNPs) across the ACE 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. Results 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, P=0.0001; rs7221780: OR 2.67, 95% CI 1.25-5.72, P=0.0003; and rs8066276: OR 3.82, 95% CI 1.80-8.13, P=0.0002; for the heterozygous variants compared with the common alleles]. None of the constructed common tag SNPs haplotypes was associated with TBI outcome. Conclusion The present study provides evidence of the possible influence of genetic variations in a specific region of the ACE gene on the outcome of TBI patients. This association may have pharmacogenetic implications in identifying those TBI patients who may benefit from ACE inhibition. ©

Original languageEnglish (US)
Pages (from-to)485-490
Number of pages6
JournalPharmacogenetics and Genomics
Volume25
Issue number10
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

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Peptidyl-Dipeptidase A
Single Nucleotide Polymorphism
Odds Ratio
Confidence Intervals
Haplotypes
Genes
Cerebrovascular Circulation
Glasgow Outcome Scale
Glasgow Coma Scale
Blood Circulation
Pharmacogenetics
Metalloproteases
Traumatic Brain Injury
Brain Injuries
Zinc
Logistic Models
Alleles
Tomography
Regression Analysis
Blood Pressure

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Effect of angiotensin-converting enzyme tag single nucleotide polymorphisms on the outcome of patients with traumatic brain injury. / Dardiotis, Efthimios; Paterakis, Konstantinos; Siokas, Vasileios; Tsivgoulis, Georgios; Dardioti, Maria; Grigoriadis, Savas; Simeonidou, Constantina; Komnos, Apostolos; Kapsalaki, Eftychia; Fountas, Kostas; Hadjigeorgiou, Georgios M.

In: Pharmacogenetics and Genomics, Vol. 25, No. 10, 01.01.2015, p. 485-490.

Research output: Contribution to journalArticle

Dardiotis, E, Paterakis, K, Siokas, V, Tsivgoulis, G, Dardioti, M, Grigoriadis, S, Simeonidou, C, Komnos, A, Kapsalaki, E, Fountas, K & Hadjigeorgiou, GM 2015, 'Effect of angiotensin-converting enzyme tag single nucleotide polymorphisms on the outcome of patients with traumatic brain injury', Pharmacogenetics and Genomics, vol. 25, no. 10, pp. 485-490. https://doi.org/10.1097/FPC.0000000000000161
Dardiotis, Efthimios ; Paterakis, Konstantinos ; Siokas, Vasileios ; Tsivgoulis, Georgios ; Dardioti, Maria ; Grigoriadis, Savas ; Simeonidou, Constantina ; Komnos, Apostolos ; Kapsalaki, Eftychia ; Fountas, Kostas ; Hadjigeorgiou, Georgios M. / Effect of angiotensin-converting enzyme tag single nucleotide polymorphisms on the outcome of patients with traumatic brain injury. In: Pharmacogenetics and Genomics. 2015 ; Vol. 25, No. 10. pp. 485-490.
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AU - Dardiotis, Efthimios

AU - Paterakis, Konstantinos

AU - Siokas, Vasileios

AU - Tsivgoulis, Georgios

AU - Dardioti, Maria

AU - Grigoriadis, Savas

AU - Simeonidou, Constantina

AU - Komnos, Apostolos

AU - Kapsalaki, Eftychia

AU - Fountas, Kostas

AU - Hadjigeorgiou, Georgios M.

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N2 - Background 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. ACE gene polymorphisms were found to regulate serum ACE enzyme activity. Objective The present study aimed to investigate possible influence of ACE gene region variants on patients' outcome after TBI. Patients and methods In total, 363 TBI patients prospectively enrolled in the study were genotyped for five tag single nucleotide polymorphisms (SNPs) across the ACE 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. Results 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, P=0.0001; rs7221780: OR 2.67, 95% CI 1.25-5.72, P=0.0003; and rs8066276: OR 3.82, 95% CI 1.80-8.13, P=0.0002; for the heterozygous variants compared with the common alleles]. None of the constructed common tag SNPs haplotypes was associated with TBI outcome. Conclusion The present study provides evidence of the possible influence of genetic variations in a specific region of the ACE gene on the outcome of TBI patients. This association may have pharmacogenetic implications in identifying those TBI patients who may benefit from ACE inhibition. ©

AB - Background 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. ACE gene polymorphisms were found to regulate serum ACE enzyme activity. Objective The present study aimed to investigate possible influence of ACE gene region variants on patients' outcome after TBI. Patients and methods In total, 363 TBI patients prospectively enrolled in the study were genotyped for five tag single nucleotide polymorphisms (SNPs) across the ACE 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. Results 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, P=0.0001; rs7221780: OR 2.67, 95% CI 1.25-5.72, P=0.0003; and rs8066276: OR 3.82, 95% CI 1.80-8.13, P=0.0002; for the heterozygous variants compared with the common alleles]. None of the constructed common tag SNPs haplotypes was associated with TBI outcome. Conclusion The present study provides evidence of the possible influence of genetic variations in a specific region of the ACE gene on the outcome of TBI patients. This association may have pharmacogenetic implications in identifying those TBI patients who may benefit from ACE inhibition. ©

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