The activity of monoamine oxidase-B (MAO-B) enzyme has a high degree of heritability, although no common genetic polymorphisms are present in the MAO-B coding region. The only known polymorphisms in MAO-B gene are a C-1, 114T in the 5' region, a variable number of GT repeats in intron 2, and a G/A change in intron 13. The genetically determined differences in MAO-B activity among subjects most likely derive from functional differences conferred by these three MAO-B genetic polymorphisms, or by polymorphisms in trans-acting factors that regulate MAO-B expression. In order to identify differences in transcriptional activity conferred by the MAO-B genetic variants, we cloned alternative alleles at the three polymorphic loci in -1,114, intron 2 and intron 13, and tested them in transfection-luciferase assays in HepG2 hepatoma and 1321N1 astrocytoma cells. The mutant -1, 114 allele T had higher activity than allele C in both cell lines, when cloned in pGL3Enhancer. Significant differences in trascriptional activity by intron 2 GT repeat allele were also observed, and varied by cell type and reporter construct. Allele G of intron 13 had significantly higher activity than allele A in both cell lines. These results indicate transcriptional activity differences between MAO-B variant alleles that are naturally occurring in the population
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