Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2001-12-12
pubmed:abstractText
The ADH3 gene encodes alcohol dehydrogenase 3 (ADH3)/glutathione-dependent formaldehyde dehydrogenase, the ancestral and most conserved form of alcohol dehydrogenase. ADH3 is expressed in all tissues examined and the enzyme is essential for formaldehyde scavenging. We have screened the promoter region including exon 1 and exons 5, 6 and 7 of the ADH3 gene for allelic variants. Using 80 samples of genomic DNA from Swedes as template, the various parts of the gene were PCR amplified and subsequently analyzed on single strand conformation polymorphism (SSCP) gels. No abnormal migration patterns could be detected by SSCP analysis of exons 5, 6 and 7 while for the promoter region, a large number of the samples displayed differences in SSCP gel migration patterns. Cloning and sequence analysis revealed four possible base pair exchanges in the promoter region. Two transitions were found at position -197 and -196, GG --> AA, one at position -79, G --> A and finally, close to the transcription start site, a fourth transition was found at position +9, C --> T. An allele specific PCR method was developed and allele frequencies were determined in three populations: Chinese, Spanish and Swedish. GG-197,-196 and AA-197,-196 alleles were common in all three populations, G-79 and A-79 were common in Swedes and Spaniards but only A-79 was found among Chinese. T+9 was the most rare allele with an allele frequency of 1.5% in Swedes. Finally, promoter activity assessments and electrophoretic mobility shift assays demonstrated that the C+9 --> T+9 exchange resulted in a significant transcriptional decrease in HeLa cells and a decreased binding of nuclear proteins. These base pair exchanges may have an effect on the expression of the enzyme and thereby influence the capacity of certain individuals to metabolize formaldehyde.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0960-314X
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
815-24
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11740346-5' Untranslated Regions, pubmed-meshheading:11740346-Adolescent, pubmed-meshheading:11740346-Adult, pubmed-meshheading:11740346-Aged, pubmed-meshheading:11740346-Aged, 80 and over, pubmed-meshheading:11740346-Aldehyde Oxidoreductases, pubmed-meshheading:11740346-Amino Acid Sequence, pubmed-meshheading:11740346-Base Sequence, pubmed-meshheading:11740346-Cell Line, pubmed-meshheading:11740346-Cell Nucleus, pubmed-meshheading:11740346-Child, pubmed-meshheading:11740346-China, pubmed-meshheading:11740346-DNA Mutational Analysis, pubmed-meshheading:11740346-Exons, pubmed-meshheading:11740346-Female, pubmed-meshheading:11740346-Gene Frequency, pubmed-meshheading:11740346-Genes, Reporter, pubmed-meshheading:11740346-HeLa Cells, pubmed-meshheading:11740346-Humans, pubmed-meshheading:11740346-Male, pubmed-meshheading:11740346-Middle Aged, pubmed-meshheading:11740346-Molecular Sequence Data, pubmed-meshheading:11740346-Polymorphism, Genetic, pubmed-meshheading:11740346-Polymorphism, Single-Stranded Conformational, pubmed-meshheading:11740346-Promoter Regions, Genetic, pubmed-meshheading:11740346-Sp1 Transcription Factor, pubmed-meshheading:11740346-Spain, pubmed-meshheading:11740346-Sweden, pubmed-meshheading:11740346-Transcription, Genetic
pubmed:year
2001
pubmed:articleTitle
Functional polymorphism in the alcohol dehydrogenase 3 (ADH3) promoter.
pubmed:affiliation
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't