COMT genotype influences the effect of alcohol on blood pressure: results from the COMBINE study.
BACKGROUND
Heavy drinking can cause chronic hypertension, possibly due to effects on the autonomic nervous system. Catechol- O-methyltransferase (COMT) inactivates catecholamines, and a G to A substitution in codon 108 in the soluble COMT mRNA (or codon 158 in the membrane-bound form) substitutes methionine for valine and alters enzyme activity.


METHODS
We evaluated the association of COMT genotype at this locus with blood pressure (BP) in 839 alcohol-dependent individuals before and during participation in an alcoholism treatment trial. Hierarchical linear models were used to account for within-subject correlation on repeated BP measurements, and findings were adjusted for age, gender, ethnicity, alcohol use, body mass index, current smoking, hypertension history, and study site.


RESULTS
Relative to those with the val-val genotype, those with the met-met genotype had higher adjusted systolic (+4.9 mm Hg, P < 0.01) and diastolic (+3.2 mm Hg, P < 0.01) BP at baseline. Those with the val-met genotype did not significantly differ from the val-val genotype. Changes in BP between baseline and 4 weeks of alcohol treatment also differed by genotype. Relative to the val-val genotype, the met-met genotype had a greater reduction in adjusted systolic pressure (-3.9 mm Hg, P < 0.01) and diastolic pressure (-2.8 mm Hg, P < 0.01). Corresponding relative reductions for the val-met genotype were -2.2 mm Hg systolic (P = 0.070) and -1.5 mm Hg diastolic (P < 0.05).


CONCLUSIONS
Findings suggest that alcohol-induced BP elevation may be related to the effects of catecholamines and their genetically determined inactivation.
Stewart
Scott H
SH
Department of Psychiatry and Behavioral Sciences, Center for Drug and Alcohol Programs, Medical University of South Carolina, Charleston, South Carolina, USA. stewarsh@musc.edu
Oroszi
Gabor
G
Randall
Patrick K
PK
Anton
Raymond F
RF
D000328:Adult; D000437:Alcoholism / Q000150:complications* / Q000201:enzymology / Q000628:therapy; D001794:Blood Pressure / Q000502:physiology*; D002394:Catechol O-Methyltransferase / Q000097:blood / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D016133:Polymerase Chain Reaction; D012307:Risk Factors
D004247:DNA; D002394:Catechol O-Methyltransferase