Role of monoamine-oxidase-A-gene variation in the development of glioblastoma in males: a case control study.
MAOA genetics glioblastoma males
Journal
Journal of neuro-oncology
ISSN: 1573-7373
Titre abrégé: J Neurooncol
Pays: United States
ID NLM: 8309335
Informations de publication
Date de publication:
Nov 2019
Nov 2019
Historique:
received:
01
08
2019
accepted:
16
09
2019
pubmed:
27
9
2019
medline:
5
6
2020
entrez:
27
9
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
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.
Identifiants
pubmed: 31556016
doi: 10.1007/s11060-019-03294-w
pii: 10.1007/s11060-019-03294-w
pmc: PMC6856259
doi:
Substances chimiques
Monoamine Oxidase
EC 1.4.3.4
monoamine oxidase A, human
EC 1.4.3.4.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
287-294Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA139020
Pays : United States
Organisme : NCI NIH HHS
ID : R01CA139020
Pays : United States
Investigateurs
Margaret R Wrensch
(MR)
Sara H Olson
(SH)
Michael E Scheurer
(ME)
Dora Il'yasova
(D)
Daniel Lachance
(D)
Georgina N Armstrong
(GN)
Lucie S McCoy
(LS)
Ching C Lau
(CC)
Elizabeth B Claus
(EB)
Jill S Barnholtz-Sloan
(JS)
Joellen Schildkraut
(J)
Francis Ali-Osman
(F)
Siegal Sadetzki
(S)
Christoffer Johansen
(C)
Richard S Houlston
(RS)
Robert B Jenkins
(RB)
Jonine L Bernstein
(JL)
Ryan T Merrell
(RT)
Faith G Davis
(FG)
Rose Lai
(R)
Sanjay Shete
(S)
Christopher I Amos
(CI)
Beatrice S Melin
(BS)
Melissa L Bondy
(ML)
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