A functional polymorphism in the monoamine oxidase A gene promoter

Abstract

We describe a new polymorphism upstream of the gene for monoamine oxidase A (MAOA), an important enzyme in human physiology and behavior. The polymorphism, which is located 1.2 kb upstream of the MAOA coding sequences, consists of a 30-bp repeated sequence present in 3, 3.5, 4, or 5 copies. The polymorphism is in linkage disequilibrium with other MAOA and MAOB gene markers and displays significant variations in allele frequencies across ethnic groups. The polymorphism has been shown to affect the transcriptional activity of the MAOA gene promoter by gene fusion and transfection experiments involving three different cell types. Alleles with 3.5 or 4 copies of the repeat sequence are transcribed 2-10 times more efficiently than those with 3 or 5 copies of the repeat, suggesting an optimal length for the regulatory region. This promoter region polymorphism may be useful as both a functional and an anonymous genetic marker for MAOA.

MAOA, maltreatment, and gene–environment interaction predicting children's mental health: new evidence and a meta-analysis

“…First, our sample comprised Caucasian twins living in England and Wales. However, allele frequencies for the MAOA promoter polymorphism 3,4 and base rates of physical abuse exposure in our sample are comparable to those reported elsewhere. 34 Future research should test whether our findings replicate in singleton children and in non-Caucasian samples.…”

“…31 In terms of expression, all studies agree on the functional classification of the two most common alleles, that is, 3-repeats (low activity), and 4-repeats (high activity). Of rare alleles, both Sabol et al 4 and Deckert et al 50 assayed the 3.5-repeat with the same result (high activity), whereas a discrepancy resulted for the 5-repeat. We chose the classification of Sabol et al 4 (i.e., 5-repeat equals low activity) as they assayed three cell lines as opposed to one.…”

“…Of rare alleles, both Sabol et al 4 and Deckert et al 50 assayed the 3.5-repeat with the same result (high activity), whereas a discrepancy resulted for the 5-repeat. We chose the classification of Sabol et al 4 (i.e., 5-repeat equals low activity) as they assayed three cell lines as opposed to one. The rare 2-repeat, of which only two cases exist in our sample, was classified as low activity based upon precedence in previous studies.…”

“…At ages 5 and 7 years, DNA samples were obtained from study members via buccal swabs and extracted using a procedure described by Freeman et al 31 Primer sequences are described by Sabol et al, 4 namely MAO APT1 (5 0 -ACAGCCTGACCGTGGA GAAG-3 0 ) and MAO APB1 (5 0 -GAACGGACGCTC CATTCGGA-3 0 ). MAO APT1 was 5 0 -labeled with the FAM fluorophore.…”

“…MAOA selectively degrades serotonin, norephinephrine, and dopamine following reuptake from the synaptic cleft, and, therefore, plays a key role in regulating behavior. 4,5 Thus far, efforts to replicate Caspi et al's 3 results have met with mixed results [6][7][8][9] indicating that, as yet, accepting the MAOA by maltreatment G Â E hypothesis would be premature without further investigation. The present study tested whether Caspi et al 3 original finding would replicate in a representative birth cohort sample of 7-year-old boys.…”