A rare truncating mutation in ADH1C (G78stop) shows significant association with Parkinson disease in a large international sample

Silvia Buervenich, Andrea Carmine, Dagmar Galter, Haydeh N. Shahabi, Bo Johnels, Björn Holmberg, Jarl Ahlberg, Hans Nissbrandt, Johanna Eerola, Olli Hellström, Pentti J. Tienari, Tohru Matsuura, Tetsuo Ashizawa, Ullrich Wüllner, Thomas Klockgether, Alexander Zimprich, Thomas Gasser, Melissa Hanson, Shamaila Waseem, Andrew SingletonFrancis J. McMahon, Maria Anvret, Olof Sydow, Lars Olson

Research output: Contribution to journalArticle

Abstract

Background: Alcohol dehydrogenases (ADHs) may be involved in the pathogenesis of neurodegenerative disorders because of their multiple roles in detoxification pathways and retinoic acid synthesis. In a previous study, significant association of an ADH class IV allele with Parkinson disease (PD) was found in a Swedish sample. Patients: The previously associated single-nucleotide polymorphism plus 12 further polymorphisms in the ADH cluster on human chromosome 4q23 were screened for association in an extension of the original sample that now included 123 Swedish PD patients and 127 geographically matched control subjects. A rare nonsense single-nucleotide polymorphism in ADH1C (G78stop, rs283413) was identified in 3 of these patients but in no controls. To obtain sufficient power to detect a possible association of this rare variant with disease, we screened a large international sample of 1076 PD patients of European ancestry and 940 matched controls. Results: The previously identified association with an ADH class IV allele remained significant (P1 2=7.5; 2-sided P=.007; odds ratio, 3.25 [95% confidence interval, 1.31-8.05]). In addition, the G78stop mutation was identified in 4 (10.0%) of 40 Caucasian index cases with PD with mainly hereditary forms of the disorder. Conclusion: Findings presented herein provide further evidence for mutations in genes encoding ADHs as genetic risk factors for PD.

Original languageEnglish (US)
Pages (from-to)74-78
Number of pages5
JournalArchives of Neurology
Volume62
Issue number1
DOIs
StatePublished - Jan 2005
Externally publishedYes

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Parkinson Disease
Alcohol Dehydrogenase
Mutation
Single Nucleotide Polymorphism
Alleles
Human Chromosomes
Tretinoin
Neurodegenerative Diseases
Odds Ratio
Alcohol
Parkinson's Disease
Confidence Intervals
Genes
Polymorphism
alcohol dehydrogenase IV
Allele

ASJC Scopus subject areas

  • Neuroscience(all)

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A rare truncating mutation in ADH1C (G78stop) shows significant association with Parkinson disease in a large international sample. / Buervenich, Silvia; Carmine, Andrea; Galter, Dagmar; Shahabi, Haydeh N.; Johnels, Bo; Holmberg, Björn; Ahlberg, Jarl; Nissbrandt, Hans; Eerola, Johanna; Hellström, Olli; Tienari, Pentti J.; Matsuura, Tohru; Ashizawa, Tetsuo; Wüllner, Ullrich; Klockgether, Thomas; Zimprich, Alexander; Gasser, Thomas; Hanson, Melissa; Waseem, Shamaila; Singleton, Andrew; McMahon, Francis J.; Anvret, Maria; Sydow, Olof; Olson, Lars.

In: Archives of Neurology, Vol. 62, No. 1, 01.2005, p. 74-78.

Research output: Contribution to journalArticle

Buervenich, S, Carmine, A, Galter, D, Shahabi, HN, Johnels, B, Holmberg, B, Ahlberg, J, Nissbrandt, H, Eerola, J, Hellström, O, Tienari, PJ, Matsuura, T, Ashizawa, T, Wüllner, U, Klockgether, T, Zimprich, A, Gasser, T, Hanson, M, Waseem, S, Singleton, A, McMahon, FJ, Anvret, M, Sydow, O & Olson, L 2005, 'A rare truncating mutation in ADH1C (G78stop) shows significant association with Parkinson disease in a large international sample', Archives of Neurology, vol. 62, no. 1, pp. 74-78. https://doi.org/10.1001/archneur.62.1.74
Buervenich, Silvia ; Carmine, Andrea ; Galter, Dagmar ; Shahabi, Haydeh N. ; Johnels, Bo ; Holmberg, Björn ; Ahlberg, Jarl ; Nissbrandt, Hans ; Eerola, Johanna ; Hellström, Olli ; Tienari, Pentti J. ; Matsuura, Tohru ; Ashizawa, Tetsuo ; Wüllner, Ullrich ; Klockgether, Thomas ; Zimprich, Alexander ; Gasser, Thomas ; Hanson, Melissa ; Waseem, Shamaila ; Singleton, Andrew ; McMahon, Francis J. ; Anvret, Maria ; Sydow, Olof ; Olson, Lars. / A rare truncating mutation in ADH1C (G78stop) shows significant association with Parkinson disease in a large international sample. In: Archives of Neurology. 2005 ; Vol. 62, No. 1. pp. 74-78.
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abstract = "Background: Alcohol dehydrogenases (ADHs) may be involved in the pathogenesis of neurodegenerative disorders because of their multiple roles in detoxification pathways and retinoic acid synthesis. In a previous study, significant association of an ADH class IV allele with Parkinson disease (PD) was found in a Swedish sample. Patients: The previously associated single-nucleotide polymorphism plus 12 further polymorphisms in the ADH cluster on human chromosome 4q23 were screened for association in an extension of the original sample that now included 123 Swedish PD patients and 127 geographically matched control subjects. A rare nonsense single-nucleotide polymorphism in ADH1C (G78stop, rs283413) was identified in 3 of these patients but in no controls. To obtain sufficient power to detect a possible association of this rare variant with disease, we screened a large international sample of 1076 PD patients of European ancestry and 940 matched controls. Results: The previously identified association with an ADH class IV allele remained significant (P1 2=7.5; 2-sided P=.007; odds ratio, 3.25 [95{\%} confidence interval, 1.31-8.05]). In addition, the G78stop mutation was identified in 4 (10.0{\%}) of 40 Caucasian index cases with PD with mainly hereditary forms of the disorder. Conclusion: Findings presented herein provide further evidence for mutations in genes encoding ADHs as genetic risk factors for PD.",
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T1 - A rare truncating mutation in ADH1C (G78stop) shows significant association with Parkinson disease in a large international sample

AU - Buervenich, Silvia

AU - Carmine, Andrea

AU - Galter, Dagmar

AU - Shahabi, Haydeh N.

AU - Johnels, Bo

AU - Holmberg, Björn

AU - Ahlberg, Jarl

AU - Nissbrandt, Hans

AU - Eerola, Johanna

AU - Hellström, Olli

AU - Tienari, Pentti J.

AU - Matsuura, Tohru

AU - Ashizawa, Tetsuo

AU - Wüllner, Ullrich

AU - Klockgether, Thomas

AU - Zimprich, Alexander

AU - Gasser, Thomas

AU - Hanson, Melissa

AU - Waseem, Shamaila

AU - Singleton, Andrew

AU - McMahon, Francis J.

AU - Anvret, Maria

AU - Sydow, Olof

AU - Olson, Lars

PY - 2005/1

Y1 - 2005/1

N2 - Background: Alcohol dehydrogenases (ADHs) may be involved in the pathogenesis of neurodegenerative disorders because of their multiple roles in detoxification pathways and retinoic acid synthesis. In a previous study, significant association of an ADH class IV allele with Parkinson disease (PD) was found in a Swedish sample. Patients: The previously associated single-nucleotide polymorphism plus 12 further polymorphisms in the ADH cluster on human chromosome 4q23 were screened for association in an extension of the original sample that now included 123 Swedish PD patients and 127 geographically matched control subjects. A rare nonsense single-nucleotide polymorphism in ADH1C (G78stop, rs283413) was identified in 3 of these patients but in no controls. To obtain sufficient power to detect a possible association of this rare variant with disease, we screened a large international sample of 1076 PD patients of European ancestry and 940 matched controls. Results: The previously identified association with an ADH class IV allele remained significant (P1 2=7.5; 2-sided P=.007; odds ratio, 3.25 [95% confidence interval, 1.31-8.05]). In addition, the G78stop mutation was identified in 4 (10.0%) of 40 Caucasian index cases with PD with mainly hereditary forms of the disorder. Conclusion: Findings presented herein provide further evidence for mutations in genes encoding ADHs as genetic risk factors for PD.

AB - Background: Alcohol dehydrogenases (ADHs) may be involved in the pathogenesis of neurodegenerative disorders because of their multiple roles in detoxification pathways and retinoic acid synthesis. In a previous study, significant association of an ADH class IV allele with Parkinson disease (PD) was found in a Swedish sample. Patients: The previously associated single-nucleotide polymorphism plus 12 further polymorphisms in the ADH cluster on human chromosome 4q23 were screened for association in an extension of the original sample that now included 123 Swedish PD patients and 127 geographically matched control subjects. A rare nonsense single-nucleotide polymorphism in ADH1C (G78stop, rs283413) was identified in 3 of these patients but in no controls. To obtain sufficient power to detect a possible association of this rare variant with disease, we screened a large international sample of 1076 PD patients of European ancestry and 940 matched controls. Results: The previously identified association with an ADH class IV allele remained significant (P1 2=7.5; 2-sided P=.007; odds ratio, 3.25 [95% confidence interval, 1.31-8.05]). In addition, the G78stop mutation was identified in 4 (10.0%) of 40 Caucasian index cases with PD with mainly hereditary forms of the disorder. Conclusion: Findings presented herein provide further evidence for mutations in genes encoding ADHs as genetic risk factors for PD.

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