Related Experiment Videos
Inheritance of low erythrocyte catechol-o-methyltransferase activity in man
Insights
Low red blood cell catechol-O-methyltransferase (RBC COMT) activity appears to be inherited in an autosomal recessive pattern. This finding suggests a genetic basis for variations in RBC COMT enzyme levels.
Area of Science:
- Biochemistry
- Human Genetics
- Pharmacogenetics
Background:
- Catechol-O-methyltransferase (COMT) is a key enzyme in neurotransmitter metabolism.
- Previous studies indicated sibling-sibling correlations in red blood cell COMT (RBC COMT) activity.
- A subgroup with low RBC COMT activity was observed in population studies.
Purpose of the Study:
- To investigate the inheritance pattern of low RBC COMT activity.
- To determine if low RBC COMT activity is genetically determined.
Main Methods:
- RBC COMT activity was measured in three cohorts: adolescents, adult blood donors, and first-degree relatives of individuals with low activity.
- Segregation analysis was performed on data from 48 families with probands exhibiting low RBC COMT activity.
Main Results:
- The distribution of RBC COMT activity in the general population was bimodal, with a nadir around 8 U.
- Approximately 23% of the randomly selected population exhibited low RBC COMT activity (< 8 U).
- Segregation analysis results were consistent with autosomal recessive inheritance of an allele for low RBC COMT activity.
Conclusions:
- The findings support an autosomal recessive inheritance model for low RBC COMT activity.
- This suggests a significant genetic component influencing RBC COMT enzyme levels in humans.
Abstract:
Catechol-O-methyltransferase activity was measured in blood obtained from 373 randomly selected subjects aged 16-18, 262 consecutive adult blood donors, and 201 first-degree relatives of subjects with RBC COMT activity of less than 8 U. The distribution of RBC COMT activity in a randoly selected populations was apparently bimodal with a nadir at approximately 8 U. Of a randomly selected population, 23% had low RBC COMT activity (less than 8 U), Because of previous reports of a significant sibling-sibling correlation of RBC COMT activity and because of the presence of a subgroup of subjects with low enzyme activity, RBC COMT activity was measured in blood from first-degree relatives of probands with low erythrocyte enzyme activity in 48 families. The results of segregation analyses of the data were compatible with autosomal recessive inheritence of an allele for low RBC COMT activity. RBC COMT in blood samples from siblings of probands inthese families also showed an apparent biomodal distribution.