title: A human fatty acid amide hydrolase (FAAH) functional gene variant is associated with lower blood pressure in young males.
abstract: BACKGROUND
  Fatty acid amide hydrolase (FAAH) inhibitors, preventing endocannabinoid (EC) degradation, reduce blood pressure (BP) and heart rate in young male (YM) hypertensive rodents. The functional human FAAH 129T gene variant results in reduced protein level and enzymatic activity but its relationship with BP is unknown. This study investigates the relationship among FAAH P129T alleles and cardiovascular features in YMs at baseline and after 9-year follow-up, and in older male obese hypertensive (OH) patients, in whom the EC system (ECS) is overactive.
  
  
  METHODS
  Genotype analysis was performed in 215 Caucasian male students (24 (0.2) years old) and in 185 older OH patients (50 (0.2) years old). YMs were also followed up for 9 years. Clinical and anthropometric variables, BP, cardiac and carotid artery echographic measurements were evaluated.
  
  
  RESULTS
  YMs with the FAAH 129T allele had lower systolic (P = 0.042) and mean BP (P = 0.022), and a trend toward lower diastolic BP (P = 0.06). Such significant association was maintained at follow-up. In contrast, the same allele was not associated with BP in older OH. No association was found with other cardiac and vascular variables.
  
  
  CONCLUSIONS
  An FAAH defective gene variant results in lower BP in YMs, similar to the findings in young rodents. This effect is lost in older OH patients. Because cannabinoid CB1 receptor blockade is associated with BP reduction in OH patients, EC effects and the use of ECS-interfering drugs is likely to be age and clinical-condition dependent.
authors.affiliation: Department of Internal Medicine, University of Ancona-Politecnica delle Marche, Ancona, Italy. r.sarzani@univpm.it
authors.forename: Riccardo
authors.initials: R
authors.lastname: Sarzani
authors.forename: Marica
authors.initials: M
authors.lastname: Bordicchia
authors.forename: Fabio
authors.initials: F
authors.lastname: Salvi
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cola
authors.forename: Eliana
authors.initials: E
authors.lastname: Franchi
authors.forename: Ilaria
authors.initials: I
authors.lastname: Battistoni
authors.forename: Lucia
authors.initials: L
authors.lastname: Mancinelli
authors.forename: Andrea
authors.initials: A
authors.lastname: Giovagnoli
authors.forename: Paolo
authors.initials: P
authors.lastname: Dessì-Fulgheri
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rappelli
mesh_terms: D000328:Adult; D000375:Aging / Q000235:genetics*; D000581:Amidohydrolases / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics*; D005500:Follow-Up Studies; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D043884:Receptor, Cannabinoid, CB1; D000099252:Fatty Acid Amide Hydrolases