Association between monoamine oxidase A activity in human male skin fibroblasts and genotype of the MAOA promoter-associated variable number tandem repeat.
Among fifteen male skin fibroblast cultures from eleven donors ranging in age from less than 1 year to 90 years old, the specific activity of monoamine oxidase A (MAO-A) differed 515-fold. Each culture had one of the two most common alleles (three or four 30-bp repeats) at the variable number tandem repeat locus positioned 1.2 kb upstream from MAOA exon 1 (uVNTR). The mean MAO-A activity in cultures with three uVNTR repeats was significantly lower than that in cultures with four repeats (1.6 +/- 1.1 and 13 +/- 12 nmol/h per milligram, respectively; P=0.032). MAO-A expression was confined to a cell sub-population varying from 0.5% to 90% of cells in different cultures. The mean specific activity in MAO-A+ cells (whole culture specific activity divided by the proportion of immunopositive cells) was lower for cultures with three repeats than for those with four (7.2 +/- 3.1 and 23.9 +/- 9.5 nmol/h per milligram protein, respectively; P=0.0013), with no overlap in activity between genotypes. Finding lower MAO-A activity in cultures with three uVNTR repeats compared to those with four is consistent with published evidence that MAO-A promoter constructs bearing three repeats have lower transcriptional activity in transfected neuroblastoma and choriocarcinoma cells. The uVNTR genotype may be a common genetic determinant of significant individual differences in oxidizing capacity for critical MAO-A substrates, which include serotonin, norepinephrine, and tyramine.
Denney
R M
RM
Department of Human Biological Chemistry and Genetics, Graduate School of Biomedical Sciences, University of Texas Medical Branch, Galveston 77555-0650, USA. rdenney@utmb.edu
Koch
H
H
Craig
I W
IW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005347:Fibroblasts / Q000201:enzymology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D008995:Monoamine Oxidase / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012867:Skin / Q000166:cytology / Q000201:enzymology*
D008995:Monoamine Oxidase