Assessment of the Role of a Functional VNTR Polymorphism in MAOA Gene Promoter: A Preliminary Study

Abstract

The monoamine oxidase A (MAOA) is involved in the degradation of various biogenic amines which have been hypothesized to have a relationship with personality traits. In literatures, however, inconsistent results appeared in a number of case-control studies using the functional MAOA-uVNTR marker. We aimed to further look into the uVNTR polymorphism among the Asian population and to preliminarily investigate its transcriptional function. Gene fusion and transfection experiments have been manipulated for the uVNTR in transfected human cervical carcinoma and neuroblastoma cell lines. For luciferase activity assay, the pGL3-Enhancer construct carrying the allele of 4 tandem repeats was chosen for protoconstruct. By using a vector-anchoring strategy, the 2-, 3-, and 5-copy alleles contained in the recombinant pGEM-T vectors were reconstructed into pGL3-Enhancer vector carrying identical core promoter sequence. Four alleles, 2-, 3-, 4-, and 5-tandem repeat, were identified from regular male Chinese Han in Taiwan (n = 474). The most common allele (3-repeat) and the second frequent one (4-repeat) constituted >99% (472 out of 474) of the observed alleles. Interestingly, in conflict with our data, the two most common alleles have an opposite ratio composition in Caucasian. Functional characterization in a luciferase assay demonstrated that the 2-repeat allele was more active than others. Together with the observation, some disagreements among the results of transcriptional activities of MAOA gene constructs were seen in literature. These discrepancies imply that the MAOA-uVNTR functional polymorphism might not play a crucial role in behavioral or physiological variability in humans. Keyword: MAOA promoter, u-VNTR, luciferase activity, antisocial behavior, forensic science