Genetic association between monoamine oxidase A microsatellite and RFLP alleles and bipolar affective disorder: analysis and meta-analysis.

The monoamine oxidase A locus (MAOA) at Xp11 was considered a good candidate to investigate in bipolar affective disorder since this enzyme plays an important role in the degradation of various neurotransmitters and a mutation in this gene has been associated with borderline mental retardation and a behavioural phenotype that has some resemblance to the manic syndrome. Previous association studies comparing allele frequencies of a microsatellite and RFLP at the monoamine oxidase A locus in bipolar affective disorder cases and controls in the UK have yielded conflicting results: Lim and colleagues reported a positive association, while no evidence for allelic association was obtained by Cradock and co-workers. A significant allelic association was observed between Japanese bipolar cases and controls at the MAOA microsatellite but different alleles seemed to be overrepresented in the bipolar cases in this population compared to the UK. In order to resolve these differences, we have examined this locus in our series of unrelated bipolar cases and age- and sex-matched controls and found significantly different MAOA microsatellite allele frequencies. In addition, we have pooled the data from the two previous UK studies with ours to create a total data set including 67 males and 113 females with bipolar affective disorder and a similar number of matched controls. No evidence for heterogeneity was observed for the control MAOA microsatellite or RFLP allele frequencies in these three studies. However, we found a significant difference between the pooled normal and bipolar allele frequencies both for the microsatellite and the RFLP at MAOA.