Alcohol dehydrogenase alleles in Parkinson's disease
Autor: | Andrea Carmine, Zhiping Zhang, Olof Sydow, Lars Olson, Silvia Buervenich, Maria Anvret |
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Rok vydání: | 2000 |
Předmět: |
Adult
Male medicine.medical_specialty DNA Mutational Analysis Biology Polymerase Chain Reaction Genetic determinism Gene Frequency Polymorphism (computer science) Internal medicine Genetic variation Odds Ratio medicine Humans Genetic Predisposition to Disease Allele Promoter Regions Genetic Alleles Aged DNA Primers Aged 80 and over Genetics Polymorphism Genetic Parkinsonism Homozygote Alcohol Dehydrogenase Parkinson Disease Odds ratio Middle Aged medicine.disease Endocrinology Neurology ADH4 ADH7 Case-Control Studies Mutation Female Neurology (clinical) Chromosomes Human Pair 4 Polymorphism Restriction Fragment Length |
Zdroj: | Movement Disorders. 15:813-818 |
ISSN: | 1531-8257 0885-3185 |
Popis: | Mutations in alcohol dehydrogenase (ADH; EC 1.1.1.1) genes may be of interest in the etiology of Parkinson's disease (PD) because of the important role these enzymes play in retinoid and dopamine metabolism and/or aldehyde detoxification. The location of several alcohol dehydrogenase genes in a cluster on chromosome 4 lends further support to ADH genes being candidates for this disorder, because recently a form of autosomal-dominant parkinsonism has been mapped to this area. We sequenced the promoter and coding regions and part of the introns of the human class IV ADH gene in 10 patients with PD. Seven different polymorphisms were identified. These polymorphisms could be assigned to four alleles (A1-A4). We then determined the frequencies of those four alleles and the wild-type allele in 78 patients with PD and 130 control subjects and found a significant association of the A1 allele with PD (odds ratio = 2.87; 95% confidence interval = 1.35-6.08). In familial cases, the association was strongest (odds ratio = 4.86; 95% confidence interval = 1.89-12.75). Two patients were homozygous for A1 whereas none of the 130 control subjects was found to be homozygous. Our results show an association between a certain ADH4 (formerly known as ADH7 in humans) allele and PD. This suggests a role for genetic variations of ADH4 as risk factors for the development of PD. Our data also show that the observed polymorphisms alone are not sufficient to cause symptoms. Further genetic and/or environmental factors have to be involved. |
Databáze: | OpenAIRE |
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