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 (P<.02) in the extended Swedish study. Furthermore, in the international collaboration, the G78stop mutation in ADH1C was found in 22 (2.0%) of the PD patients but only in 6 controls (0.6%). This association was statistically significant (chi(2)(1) = 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.
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 PDpatients 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 PDpatients of European ancestry and 940 matched controls. RESULTS: The previously identified association with an ADH class IV allele remained significant (P<.02) in the extended Swedish study. Furthermore, in the international collaboration, the G78stop mutation in ADH1C was found in 22 (2.0%) of the PDpatients but only in 6 controls (0.6%). This association was statistically significant (chi(2)(1) = 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.
Authors: Parvoneh Poorkaj; Wendy H Raskind; James B Leverenz; Mark Matsushita; Cyrus P Zabetian; Ali Samii; Sophia Kim; Nayiry Gazi; John G Nutt; John Wolff; Dora Yearout; J Lynne Greenup; Ellen J Steinbart; Thomas D Bird Journal: Mov Disord Date: 2010-07-30 Impact factor: 10.338
Authors: Xingguang Luo; Henry R Kranzler; Lingjun Zuo; Huiping Zhang; Shuang Wang; Joel Gelernter Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2008-03-05 Impact factor: 3.568
Authors: Deepak Kumar Bhatt; Andrea Gaedigk; Robin E Pearce; J Steven Leeder; Bhagwat Prasad Journal: Drug Metab Dispos Date: 2017-06-12 Impact factor: 3.922