Abstract
BackgroundThe Mono-amine oxidase-A (MAO-A) enzyme is involved in the degradation and regulation of catecholamines such as serotonin, dopamine, epinephrine and nor-epinephrine. Preclinical studies suggest that this enzyme may contribute to an environment favorable for growth of malignant glioma. The MAO-A gene is located on the X-chromosome and has at least one functional genetic polymorphism. The aim of the present study was to explore possible effects of MAO-A genotype on development of glioblastoma in males.MethodsGenotypes for 437 glioma cases and 876 population-based controls from the Swedish Glioma International Case–Control study (GICC) were compared. We analyzed the germline DNA using the Illumina Oncoarray. We selected seven single nucleotide polymorphisms (SNPs) located in the MAO-A gene, and imputed genotypes based on data from the 1000 genomes project. We used 1579 male glioblastoma cases and 1875 controls comprising the whole GICC cohort for subsequent validation of findings.ResultsThe rs144551722 SNP was a significant predictor of development of glioblastoma in males (p-value = 0.0056) but not in females even after correction for multiple testing. We conducted haplotype analysis to confirm an association between MAO-A gene and risk of glioblastoma (p-value = 0.016). We found similar results in the validation sample.ConclusionsThese results suggest the possibility of a role for the MAO-A enzyme and the MAO-A gene in the development of glioblastoma in males.
Highlights
The risk for developing glioma is roughly 1.4 times greater for males than females [1, 2]
The study subjects included in the risk analysis were those who participated in the Swedish Glioma International Case–Control (GICC) study
The purpose of the present study was to investigate the hypothesis that polymorphisms in the Mono-amine oxidase-A (MAO-A)-gene are associated with development of glioma in males
Summary
The risk for developing glioma is roughly 1.4 times greater for males than females [1, 2]. A recent study using a similar approach but focusing on the X-chromosome identified four regions of potential interest that remained statistically significant after correction for 250,000 significance tests [4]. In these studies, an agnostic, exploratory methodology was applied, according to which all available polymorphisms were analyzed, regardless of known function. A potential useful alternative strategy in the study of genetically determined sex differences is the candidate gene study In this context such a strategy might mean focusing on known x-linked genetic polymorphisms that, for theoretical reasons, might be expected to be related to glioma development. Conclusions These results suggest the possibility of a role for the MAO-A enzyme and the MAO-A gene in the development of glioblastoma in males
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