A human fatty acid amide hydrolase (FAAH) functional gene variant is associated with lower blood pressure in young males.
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.
Sarzani
Riccardo
R
Department of Internal Medicine, University of Ancona-Politecnica delle Marche, Ancona, Italy. r.sarzani@univpm.it
Bordicchia
Marica
M
Salvi
Fabio
F
Cola
Giovanna
G
Franchi
Eliana
E
Battistoni
Ilaria
I
Mancinelli
Lucia
L
Giovagnoli
Andrea
A
Dessì-Fulgheri
Paolo
P
Rappelli
Alessandro
A
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
D000581:Amidohydrolases; D043884:Receptor, Cannabinoid, CB1; D000099252:Fatty Acid Amide Hydrolases