Association between the low activity genotype of catechol-O-methyltransferase and myocardial infarction in a hypertensive population.
OBJECTIVE
Estrogens regulate several biological processes involved in the pathogenesis of myocardial infarction. Catechol-O-methyltransferase (COMT) is a key enzyme in the degradation of estrogens. There is a functional polymorphism in the COMT gene (Val158Met), affecting the activity of the enzyme. We investigated if the low activity genotype of COMT is associated with an altered risk of myocardial infarction.


RESULTS
In a prospectively followed hypertensive cohort we identified 174 patients who suffered a myocardial infarction during the study and compared them to 348 controls from the same cohort. The COMT polymorphism and serum levels of sex hormones were analysed. Patients homozygous for the low activity COMT genotype had a decreased risk of myocardial infarction compared to those with the high activity genotype, odds ratio 0.65 (95% CI 0.44-0.97, p=0.033 ). The protective effect of the low activity genotype was most evident among older patients (> 58 years of age), odds ratio 0.43 (95% CI 0.23-0.79, p=0.006 ). Serum levels of estradiol were increased ( p=0.006 ) in males with the low activity genotype.


CONCLUSIONS
Our findings suggest that the low activity COMT genotype is protective against myocardial infarction. One may speculate that the altered estrogen status could be involved in this effect.
Eriksson
Anna-Lena
AL
Division of Clinical Pharmacology, Department of Internal Medicine, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden.
Skrtic
Stanko
S
Niklason
Anders
A
Hultén
Lillemor Mattsson
LM
Wiklund
Olov
O
Hedner
Thomas
T
Ohlsson
Claes
C
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002216:Captopril / Q000627:therapeutic use*; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000201:enzymology / Q000235:genetics*; D011110:Polymorphism, Genetic; D011446:Prospective Studies
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D002394:Catechol O-Methyltransferase