title: The effect of a single nucleotide polymorphism of the CYP4F2 gene on blood pressure and 20-hydroxyeicosatetraenoic acid excretion after weight loss.
abstract: BACKGROUND
  Genetic background partly determines the efficacy of interventions to lower blood pressure (BP). The CYP4F2 and CYP4A11 enzymes are renal 20-hydroxyeicosatetraenoic acid (20-HETE) synthases that regulate BP. Gene variants of CYP4F2 and CYP4A11 associate with hypertension and stroke. We showed that a gene variant of CYP4F2 but not CYP4A11 was associated with increased 20-HETE excretion and BP.
  
  
  OBJECTIVE
  To compare BP and 20-HETE responses in carriers of the CYP4F2 1347G/A polymorphism and controls CYP4F2-GG (wildtype), during weight loss.
  
  
  METHODS
  Volunteers genotyped as CYP4F2GA/AA (n = 26) and controls genotyped as CYP4F2 GG (n = 27) were counselled to reduce weight for 12 weeks, followed by 4 weeks of weight stabilization. Weight, 24-h BP, pulse pressure and urinary 20-HETE were measured at baseline, 12 and 16 weeks.
  
  
  RESULTS
  At baseline, SBP was (+1.7 mmHg, P = 0.047) in the CYP4F2 GA/AA genotype. Compared with baseline, weight fell by 3.9 kg, P = 0.0001, in both genotypes, and was maintained to 16 weeks. SBP fell by (-7.6 mmHg, P = 0.004) in both genotypes after 12 weeks. However, after weight stabilization, SBP was +3.6 mmHg, P = 0.004 in CYP4F2 GA/AA genotype. DBP and heart rate changed similarly over time. Pulse pressure fell with weight loss (P < 0.001), but was elevated in the CYP4F2 GA/AA genotype at all time-points (+3.1 mmHg, P < 0.001). Urinary 20-HETE was similar at baseline and 12 weeks but elevated in the CYP4F2 GA/AA genotype (P = 0.017) after weight stabilization.
  
  
  CONCLUSIONS
  Maintenance of lower BP after weight loss is more difficult for carriers of the CYP4F2 G1347A polymorphism and may be related to increased arterial stiffness and increased 20-HETE synthesis.
authors.affiliation: aUniversity of Western Australia, School of Medicine & Pharmacology, Royal Perth Hospital bSchool of Surgery and Pathology cWestern Australian Institute for Medical Research, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Natalie C
authors.initials: NC
authors.lastname: Ward
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Croft
authors.forename: Ian B
authors.initials: IB
authors.lastname: Puddey
authors.forename: Michael
authors.initials: M
authors.lastname: Phillips
authors.forename: Frank
authors.initials: F
authors.lastname: van Bockxmeer
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Beilin
authors.forename: Anne E
authors.initials: AE
authors.lastname: Barden
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000235:genetics* / Q000502:physiology*; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000502:physiology*; D000072470:Cytochrome P450 Family 4; D005260:Female; D056726:Genetic Association Studies; D006339:Heart Rate / Q000235:genetics / Q000502:physiology; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood / Q000652:urine*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D050177:Overweight / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D020641:Polymorphism, Single Nucleotide; D059289:Vascular Stiffness / Q000235:genetics / Q000502:physiology; D015431:Weight Loss / Q000235:genetics* / Q000502:physiology*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D006893:Hydroxyeicosatetraenoic Acids; D008055:Lipids; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; C465478:CYP4A11 protein, human; D042926:Cytochrome P-450 CYP4A