title: Oestrogen receptor gene variation is a determinant of coronary reactivity in healthy young men.
abstract: BACKGROUND
  Oxidised low-density lipoprotein (ox-LDL) is a determinant of impaired coronary function and oestrogens inhibit its formation probably throughout genetically-variable oestrogen receptor 1 (ESR1) in artery wall. We hypothesized that the ESR1 polymorphism might influence coronary function and reactivity as measured by positron emission tomography (PET), which allows the detection of coronary dysfunction before appearance of angiographic lesions.
  
  
  METHODS
  Fifty-one healthy young men (aged 35 +/- 4 years), with normal or slightly-elevated serum cholesterol, underwent PET with intravenous adenosine. ESR1 PvuII genotypes P/P, P/p, and p/p in addition to the plasma autoantibody titre against ox-LDL, a marker of in vivo oxidation, were determined.
  
  
  RESULTS
  The ESR1 genotype persisted as the only significant predictor of adenosine stimulated coronary flow (P = 0.035) after adjustment for other coronary risk factors. Subjects with P/P genotype had 33.4 and 41.8% lower adenosine-stimulated flow values than subjects with P/p and p/p genotypes (P = 0.030). Furthermore, plasma levels of ox-LDL titre were on average 59 and 77% higher in subjects with P/P genotype than in subjects with P/p or p/p genotypes (P = 0.049).
  
  
  CONCLUSIONS
  These tentative findings from our pilot study provide evidence that genetic variation in ESR1 may modify coronary reactivity and LDL oxidation and reflect differences in the early pathogenesis of coronary dysfunction in these healthy young men.
authors.affiliation: Department of Clinical hemistry, Centre for Laboratory Medicine, Tampere University Hospital and Tampere University Medical School, Tampere, Finland. bltele@uta.fi
authors.forename: T
authors.initials: T
authors.lastname: Lehtimäki
authors.forename: R
authors.initials: R
authors.lastname: Laaksonen
authors.forename: K M
authors.initials: KM
authors.lastname: Mattila
authors.forename: T
authors.initials: T
authors.lastname: Janatuinen
authors.forename: R
authors.initials: R
authors.lastname: Vesalainen
authors.forename: P
authors.initials: P
authors.lastname: Nuutila
authors.forename: J
authors.initials: J
authors.lastname: Laakso
authors.forename: O
authors.initials: O
authors.lastname: Jaakkola
authors.forename: T
authors.initials: T
authors.lastname: Koivula
authors.forename: J
authors.initials: J
authors.lastname: Knuuti
mesh_terms: D000328:Adult; D001794:Blood Pressure; D002320:Cardiovascular Physiological Phenomena; D002784:Cholesterol / Q000097:blood; D003326:Coronary Circulation / Q000502:physiology; D047628:Estrogen Receptor alpha; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D008297:Male; D010084:Oxidation-Reduction; D011110:Polymorphism, Genetic; D011960:Receptors, Estrogen / Q000235:genetics*; D014055:Tomography, Emission-Computed; D014280:Triglycerides / Q000097:blood
chemical_list: D047628:Estrogen Receptor alpha; D008074:Lipoproteins; D011960:Receptors, Estrogen; D014280:Triglycerides; D002784:Cholesterol