TY - JOUR
T1 - Role of monoamine-oxidase-A-gene variation in the development of glioblastoma in males
T2 - a case control study
AU - The Gliogene Group
AU - Sjöberg, Rickard L.
AU - Wu, Wendy Yi Ying
AU - Dahlin, Anna M.
AU - Tsavachidis, Spiridon
AU - Bondy, Melissa L.
AU - Melin, Beatrice
AU - Wrensch, Margaret R.
AU - Olson, Sara H.
AU - Scheurer, Michael E.
AU - Il’yasova, Dora
AU - Lachance, Daniel
AU - Armstrong, Georgina N.
AU - McCoy, Lucie S.
AU - Lau, Ching C.
AU - Claus, Elizabeth B.
AU - Barnholtz-Sloan, Jill S.
AU - Schildkraut, Joellen
AU - Ali-Osman, Francis
AU - Sadetzki, Siegal
AU - Johansen, Christoffer
AU - Houlston, Richard S.
AU - Jenkins, Robert B.
AU - Bernstein, Jonine L.
AU - Merrell, Ryan T.
AU - Davis, Faith G.
AU - Lai, Rose
AU - Shete, Sanjay
AU - Amos, Christopher I.
AU - Melin, Beatrice S.
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Background: The 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. Methods: Genotypes 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. Results: The 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. 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.
AB - Background: The 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. Methods: Genotypes 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. Results: The 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. 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.
KW - MAOA genetics glioblastoma males
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U2 - 10.1007/s11060-019-03294-w
DO - 10.1007/s11060-019-03294-w
M3 - Article
C2 - 31556016
AN - SCOPUS:85075091744
SN - 0167-594X
VL - 145
SP - 287
EP - 294
JO - Journal of neuro-oncology
JF - Journal of neuro-oncology
IS - 2
ER -