Histamine N-methyltransferase Thr105Ile polymorphism is associated with Parkinson's disease

Vinko Palada; Janoš Terzić; Joseph Mazzulli; Grace Bwala; Johann Hagenah; Borut Peterlin; Albert Y. Hung; Christine Klein; Dimitri Krainc

doi:10.1016/j.neurobiolaging.2011.06.015

Histamine N-methyltransferase Thr105Ile polymorphism is associated with Parkinson's disease

Vinko Palada, Janoš Terzić, Joseph Mazzulli, Grace Bwala, Johann Hagenah, Borut Peterlin, Albert Y. Hung, Christine Klein, Dimitri Krainc^*

^*Corresponding author for this work

Neurology

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

Abstract

Histamine is a central neurotransmitter degraded by histamine-N-methyltransferase (HNMT). Several abnormalities in the histaminergic system were found in patients with Parkinson's disease (PD), thus we tested the possible association of a Thr105Ile functional polymorphism in HNMT with PD. A total of 913 patients with PD and 958 controls were genotyped using a TaqMan RT-PCR Genotyping Assay (Foster City, California, USA). Lower frequency of HNMT Ile105 allele that is associated with decreased enzymatic activity was found in patients compared with controls (χ² = 11.65; p = 0.0006). We performed meta-analysis to confirm the association of Thr105Ile functional polymorphism with PD. Our results indicate that lower HNMT activity plays a role in the pathogenesis of PD.

Original language	English (US)
Pages (from-to)	836.e1-836.e3
Journal	Neurobiology of Aging
Volume	33
Issue number	4
DOIs	https://doi.org/10.1016/j.neurobiolaging.2011.06.015
State	Published - Apr 2012

Funding

This study was sponsored by National Parkinson Foundation (DK), GENEPARK ( EU-LSHB-CT-2006-037544 ) grant (DK), Volkswagen Foundation, Hermann and Lilly Schilling Foundation, and NGFN Plus PNP-01GS08135-3 (BMBF, CK). Dr. Johann Hagenah receives research support from the Bachmann-Strauss Dystonia Parkinson Foundation and received honoraria as an invited speaker from GlaxoSmithKline. Dr. Christine Klein received consulting fees from Boehringer Ingelheim and Centogene and received honoraria for speaking from Boehringer Ingelheim and Merz Pharma. Dr. Klein is the recipient of a career development award from the Hermann and Lilly Schilling Foundation. She is funded by the Volkswagen Foundation, the Deutsche Forschungsgemeinschaft, the Possehl Foundation and received institutional support from the University of Lübeck for genetics research. Dr. Dimitri Krainc receives research support from Novartis Pharma. The remaining authors disclose no conflicts of interest.

Keywords

Association studies in genetics
HNMT
Histamine
Parkinson's disease
Parkinsonism

ASJC Scopus subject areas

General Neuroscience
Aging
Developmental Biology
Clinical Neurology
Geriatrics and Gerontology

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10.1016/j.neurobiolaging.2011.06.015

Cite this

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title = "Histamine N-methyltransferase Thr105Ile polymorphism is associated with Parkinson's disease",

abstract = "Histamine is a central neurotransmitter degraded by histamine-N-methyltransferase (HNMT). Several abnormalities in the histaminergic system were found in patients with Parkinson's disease (PD), thus we tested the possible association of a Thr105Ile functional polymorphism in HNMT with PD. A total of 913 patients with PD and 958 controls were genotyped using a TaqMan RT-PCR Genotyping Assay (Foster City, California, USA). Lower frequency of HNMT Ile105 allele that is associated with decreased enzymatic activity was found in patients compared with controls (χ2 = 11.65; p = 0.0006). We performed meta-analysis to confirm the association of Thr105Ile functional polymorphism with PD. Our results indicate that lower HNMT activity plays a role in the pathogenesis of PD.",

keywords = "Association studies in genetics, HNMT, Histamine, Parkinson's disease, Parkinsonism",

author = "Vinko Palada and Jano{\v s} Terzi{\'c} and Joseph Mazzulli and Grace Bwala and Johann Hagenah and Borut Peterlin and Hung, {Albert Y.} and Christine Klein and Dimitri Krainc",

note = "Funding Information: This study was sponsored by National Parkinson Foundation (DK), GENEPARK ( EU-LSHB-CT-2006-037544 ) grant (DK), Volkswagen Foundation, Hermann and Lilly Schilling Foundation, and NGFN Plus PNP-01GS08135-3 (BMBF, CK). Funding Information: Dr. Johann Hagenah receives research support from the Bachmann-Strauss Dystonia Parkinson Foundation and received honoraria as an invited speaker from GlaxoSmithKline. Dr. Christine Klein received consulting fees from Boehringer Ingelheim and Centogene and received honoraria for speaking from Boehringer Ingelheim and Merz Pharma. Dr. Klein is the recipient of a career development award from the Hermann and Lilly Schilling Foundation. She is funded by the Volkswagen Foundation, the Deutsche Forschungsgemeinschaft, the Possehl Foundation and received institutional support from the University of L{\"u}beck for genetics research. Dr. Dimitri Krainc receives research support from Novartis Pharma. The remaining authors disclose no conflicts of interest. ",

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doi = "10.1016/j.neurobiolaging.2011.06.015",

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AU - Palada, Vinko

AU - Terzić, Janoš

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AU - Bwala, Grace

AU - Hagenah, Johann

AU - Peterlin, Borut

AU - Hung, Albert Y.

AU - Klein, Christine

AU - Krainc, Dimitri

N1 - Funding Information: This study was sponsored by National Parkinson Foundation (DK), GENEPARK ( EU-LSHB-CT-2006-037544 ) grant (DK), Volkswagen Foundation, Hermann and Lilly Schilling Foundation, and NGFN Plus PNP-01GS08135-3 (BMBF, CK). Funding Information: Dr. Johann Hagenah receives research support from the Bachmann-Strauss Dystonia Parkinson Foundation and received honoraria as an invited speaker from GlaxoSmithKline. Dr. Christine Klein received consulting fees from Boehringer Ingelheim and Centogene and received honoraria for speaking from Boehringer Ingelheim and Merz Pharma. Dr. Klein is the recipient of a career development award from the Hermann and Lilly Schilling Foundation. She is funded by the Volkswagen Foundation, the Deutsche Forschungsgemeinschaft, the Possehl Foundation and received institutional support from the University of Lübeck for genetics research. Dr. Dimitri Krainc receives research support from Novartis Pharma. The remaining authors disclose no conflicts of interest.

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N2 - Histamine is a central neurotransmitter degraded by histamine-N-methyltransferase (HNMT). Several abnormalities in the histaminergic system were found in patients with Parkinson's disease (PD), thus we tested the possible association of a Thr105Ile functional polymorphism in HNMT with PD. A total of 913 patients with PD and 958 controls were genotyped using a TaqMan RT-PCR Genotyping Assay (Foster City, California, USA). Lower frequency of HNMT Ile105 allele that is associated with decreased enzymatic activity was found in patients compared with controls (χ2 = 11.65; p = 0.0006). We performed meta-analysis to confirm the association of Thr105Ile functional polymorphism with PD. Our results indicate that lower HNMT activity plays a role in the pathogenesis of PD.

AB - Histamine is a central neurotransmitter degraded by histamine-N-methyltransferase (HNMT). Several abnormalities in the histaminergic system were found in patients with Parkinson's disease (PD), thus we tested the possible association of a Thr105Ile functional polymorphism in HNMT with PD. A total of 913 patients with PD and 958 controls were genotyped using a TaqMan RT-PCR Genotyping Assay (Foster City, California, USA). Lower frequency of HNMT Ile105 allele that is associated with decreased enzymatic activity was found in patients compared with controls (χ2 = 11.65; p = 0.0006). We performed meta-analysis to confirm the association of Thr105Ile functional polymorphism with PD. Our results indicate that lower HNMT activity plays a role in the pathogenesis of PD.

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Histamine N-methyltransferase Thr105Ile polymorphism is associated with Parkinson's disease

Abstract

Funding

Keywords

ASJC Scopus subject areas

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