title: Association of a functional polymorphism in the CYP4A11 gene with systolic blood pressure in survivors of myocardial infarction.
abstract: OBJECTIVE
  Survivors of myocardial infarction (MI) are known to have a high prevalence of arterial hypertension which, at the same time, imposes a major risk to such patients. Genetic variants of the arachidonic acid monooxygenase CYP4A11 may result in decreased synthesis of 20-hydroxyeicostatetraenoic acid (20-HETE), experimental hypertension and elevated blood pressure levels in humans. The present study aimed to investigate the impact of the functionally relevant T8590C polymorphism of this gene on blood pressure and the prevalence of hypertension in MI patients.
  
  
  METHODS
  Survivors of MI from the MONICA Augsburg MI registry (n = 560) were studied after a mean of 5.6 years after the acute event. Participants were examined by standardized anthropometric and echocardiographic measurements, as well as genotyping for CYP4A11 T8590C allele status.
  
  
  RESULTS
  Genotype frequencies in MI patients (TT = 71.8%, CT = 26.2%, CC = 2.0%) did not differ from those in population-based controls (n = 1363; TT = 75.4%, CT = 22.5% and CC = 2.1%, P = 0.22). MI survivors with the CC genotype displayed higher systolic blood pressure levels (CC: 143.4 +/- 4.9 mmHg versus CT: 134.5 +/- 1.3 mmHg and TT: 131.1 +/- 0.8 mmHg; P = 0.02) and a non-significant trend towards higher diastolic blood pressure levels (CC: 88.4 +/- 3.0 mmHg versus CT: 84.9 +/- 0.8 mmHg and TT: 83.9 +/- 0.5 mmHg; P = 0.17) in multivariate models. Accordingly, the C allele was related to elevated odds ratios for hypertension in a recessive [4.14; 95% confidence interval (CI) = 1.07-15.96, P = 0.04] and in a dominant model (1.50; 95% CI = 1.03-2.20, P = 0.04), respectively. No blood pressure-independent association of the T8590C polymorphism with echocardiographic parameters of left ventricular function and/or geometry was found.
  
  
  CONCLUSIONS
  The data obtained in the present study strengthen the evidence of an association of the CYP4A11 T8590C polymorphism with blood pressure levels and hypertension prevalence. Particularly, the risk of arterial hypertension is substantially higher in MI patients homozygous for the CC allele. By contrast, no evidence was obtained for an association between this genotype and MI.
authors.affiliation: Medizinische Klinik II, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Mayer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lieb
authors.forename: Anika
authors.initials: A
authors.lastname: Götz
authors.forename: Inke R
authors.initials: IR
authors.lastname: König
authors.forename: Lena F
authors.initials: LF
authors.lastname: Kauschen
authors.forename: Patrick
authors.initials: P
authors.lastname: Linsel-Nitschke
authors.forename: Andrea
authors.initials: A
authors.lastname: Pomarino
authors.forename: Stephan
authors.initials: S
authors.lastname: Holmer
authors.forename: Christian
authors.initials: C
authors.lastname: Hengstenberg
authors.forename: Angela
authors.initials: A
authors.lastname: Doering
authors.forename: Hannelore
authors.initials: H
authors.lastname: Loewel
authors.forename: Hans-Werner
authors.initials: HW
authors.lastname: Hense
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
authors.forename: Jeanette
authors.initials: J
authors.lastname: Erdmann
authors.forename: Heribert
authors.initials: H
authors.lastname: Schunkert
mesh_terms: D016022:Case-Control Studies; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005838:Genotype; D006352:Heart Ventricles / Q000000981:diagnostic imaging; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D017741:Survivors; D014463:Ultrasonography
chemical_list: D003577:Cytochrome P-450 Enzyme System; C465478:CYP4A11 protein, human; D042926:Cytochrome P-450 CYP4A