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Homozygosity for the EPHX2 K55R polymorphism increases the long-term risk of ischemic stroke in men: a study in Swedes.

Fava, Cristiano LU ; Montagnana, Martina LU ; Danese, Elisa; Almgren, Peter LU ; Hedblad, Bo LU ; Engström, Gunnar LU ; Berglund, Göran LU ; Minuz, Pietro and Melander, Olle LU (2010) In Pharmacogenetics & Genomics 20(2). p.94-103
Abstract
OBJECTIVES: The soluble epoxide hydrolase (gene name EPHX2) is responsible for metabolism of 8,9 11,12 and 14,15-epoxyeicosatrienoic acids, vasodilator and anti-inflammatory substances. There are several functional polymorphisms in the EPHX2 gene: two of them, the K55R and R287Q, showing an altered metabolic activity in vitro, were associated with coronary heart disease and ischemic stroke in previous studies. The aim of this study was to evaluate the effect of four polymorphisms in the EPHX2 gene on blood pressure levels, hypertension prevalence, and risk of incident cardiovascular events in a large sample of middle-aged Swedes. METHODS: The incidence of cardiovascular events (coronary events, n = 274; ischemic stroke, n = 197) was... (More)
OBJECTIVES: The soluble epoxide hydrolase (gene name EPHX2) is responsible for metabolism of 8,9 11,12 and 14,15-epoxyeicosatrienoic acids, vasodilator and anti-inflammatory substances. There are several functional polymorphisms in the EPHX2 gene: two of them, the K55R and R287Q, showing an altered metabolic activity in vitro, were associated with coronary heart disease and ischemic stroke in previous studies. The aim of this study was to evaluate the effect of four polymorphisms in the EPHX2 gene on blood pressure levels, hypertension prevalence, and risk of incident cardiovascular events in a large sample of middle-aged Swedes. METHODS: The incidence of cardiovascular events (coronary events, n = 274; ischemic stroke, n = 197) was monitored over 10 years of follow-up. RESULTS: In the whole population, all polymorphisms had no effect on the studied parameters but a positive interaction between male sex and three SNPs including the K55R was evident: male, but not female, EPHX2 R55R homozygotes had significantly higher crude and adjusted systolic blood pressure and higher hypertension prevalence with respect to K-carriers. Kaplan-Meier curves showed higher incidence of ischemic strokes in male R55R homozygotes with respect to K-carriers (P = 0.015 by log-rank test). After adjustment for major cardiovascular risk factors, the hazard ratio for incident ischemic stroke in male R55R homozygotes remained significantly higher (hazard ratio: 4.8; 95% confidence interval: 1.2-19.9). CONCLUSION: The functional K55R polymorphism of the EPHX2 gene confers a higher risk of hypertension prevalence and increases the risk of incident ischemic stroke in male homozygotes. Additional studies are needed to confirm these data and to elucidate the interaction between sex and the EPHX2 K55R polymorphism. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Pharmacogenetics & Genomics
volume
20
issue
2
pages
94 - 103
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000274306700004
  • pmid:20065888
  • scopus:75649101239
ISSN
1744-6872
DOI
10.1097/FPC.0b013e3283349ec9
language
English
LU publication?
yes
id
a5611cac-3a47-479c-867d-62af66c56145 (old id 1541183)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20065888?dopt=Abstract
date added to LUP
2010-02-02 12:58:50
date last changed
2018-05-29 11:37:53
@article{a5611cac-3a47-479c-867d-62af66c56145,
  abstract     = {OBJECTIVES: The soluble epoxide hydrolase (gene name EPHX2) is responsible for metabolism of 8,9 11,12 and 14,15-epoxyeicosatrienoic acids, vasodilator and anti-inflammatory substances. There are several functional polymorphisms in the EPHX2 gene: two of them, the K55R and R287Q, showing an altered metabolic activity in vitro, were associated with coronary heart disease and ischemic stroke in previous studies. The aim of this study was to evaluate the effect of four polymorphisms in the EPHX2 gene on blood pressure levels, hypertension prevalence, and risk of incident cardiovascular events in a large sample of middle-aged Swedes. METHODS: The incidence of cardiovascular events (coronary events, n = 274; ischemic stroke, n = 197) was monitored over 10 years of follow-up. RESULTS: In the whole population, all polymorphisms had no effect on the studied parameters but a positive interaction between male sex and three SNPs including the K55R was evident: male, but not female, EPHX2 R55R homozygotes had significantly higher crude and adjusted systolic blood pressure and higher hypertension prevalence with respect to K-carriers. Kaplan-Meier curves showed higher incidence of ischemic strokes in male R55R homozygotes with respect to K-carriers (P = 0.015 by log-rank test). After adjustment for major cardiovascular risk factors, the hazard ratio for incident ischemic stroke in male R55R homozygotes remained significantly higher (hazard ratio: 4.8; 95% confidence interval: 1.2-19.9). CONCLUSION: The functional K55R polymorphism of the EPHX2 gene confers a higher risk of hypertension prevalence and increases the risk of incident ischemic stroke in male homozygotes. Additional studies are needed to confirm these data and to elucidate the interaction between sex and the EPHX2 K55R polymorphism.},
  author       = {Fava, Cristiano and Montagnana, Martina and Danese, Elisa and Almgren, Peter and Hedblad, Bo and Engström, Gunnar and Berglund, Göran and Minuz, Pietro and Melander, Olle},
  issn         = {1744-6872},
  language     = {eng},
  number       = {2},
  pages        = {94--103},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Pharmacogenetics & Genomics},
  title        = {Homozygosity for the EPHX2 K55R polymorphism increases the long-term risk of ischemic stroke in men: a study in Swedes.},
  url          = {http://dx.doi.org/10.1097/FPC.0b013e3283349ec9},
  volume       = {20},
  year         = {2010},
}