Association of Monoamine Oxidase A Gene Promoter Region (30 bp μVNTR) Polymorphism with Serum Levels in Multiple Psychiatric Disorders

Background: Monoamine oxidase A (MAOA) has a role in metabolising different biogenic amines, including dopamine. Functional studies have revealed the effect of promoter region variants on the transcriptional activity of the MAOA that consequently affects the homeostasis of the biogenic amines which might implicate in the aetiology of multiple psychiatric conditions. Objectives: The current study aimed to determine the influence of the promoter region 30 base pair (bp), a variable number of tandem repeats (VNTR) of the MAOA, on its serum levels and association with schizophrenia (SHZ), bipolar disorder (BD), and major depressive disorder (MDD) in the Pakistani population. Methods: A total of 1062 subjects [MDD n = 416, BD n = 200, SHZ n = 97 and controls n = 349], were genotyped for MAOA-30bp µVNTR through standard polymerase chain reaction technique and logistic regression was applied to determine the genetic association. Serum MAOA levels were determined through enzyme-linked immunosorbent assay (ELISA) and the Mann-Whitney U test was applied. Results: In genotype analysis, eight different repeat (R) alleles of MAOA-30 bp µVNTR were observed, where 4.5R, 5.5R, and 6R were the rare repeats found in the current Pakistani cohort. In serum-based analysis the total MAOA serum levels were found to be significantly elevated in SHZ; however, in sub-group analysis, significantly higher serum levels of MAOA were observed only in the rare allele groups of MDD, BD, and SHZ. Conclusions: The current study gives us further insights into the complex nature of MAOA regulation and its genetic and serum-levels association with different psychiatric conditions.