A FUNCTIONAL POLYMORPHISM IN THE MONOAMINE-OXIDASE-A GENE PROMOTER

We describe a new polymorphism upstream of the gene for monoamine oxid ase A (MAOA), an important enzyme in human physiology and behavior. Th e polymorphism, which is located 1.2 kb upstream of the MAOA coding se quences, consists of a 30-bp repeated sequence present in 3, 3.5, 4, o r 5 copies. The polymorphism is in linkage disequilibrium with other M AOA and MAOB gene markers and displays significant variations in allel e 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 ty pes. Alleles with 3.5 or 4 copies of the repeat sequence are transcrib ed 2-10 times more efficiently than those with 3 or 5 copies of the re peat, suggesting an optimal length for the regulatory region. This pro moter region polymorphism may be useful as both a functional and an an onymous genetic marker for MAOA.