title: Genetic polymorphisms in the formaldehyde dehydrogenase gene and their biological significance.
abstract: The GSH-dependent formaldehyde dehydrogenase (FDH) is the most important enzyme for the metabolic inactivation of formaldehyde. We studied three polymorphisms of this gene with the intention to elucidate their relevance for inter-individual differences in the protection against the (geno-)toxicity of FA. The first polymorphism (rs11568816) was investigated using real-time PCR and restriction fragment analysis in 150 subjects. However, we did not find the polymorphic sequence in any of the subjects. We studied a second polymorphism (rs17028487), representing a base exchange (c.*114A>G) in exon 9 of the FDH gene. We analyzed 70 subjects with the SNaPshot Primer Extension method and subsequent analysis in a ABI PRISM 3100, but no variant allele was identified. A third polymorphism, rs13832 in exon 9 (c.*493G>T), was studied in a group of 105 subjects by the SNaPshot Primer Extension method. 43 of the subjects were heterozygous for the polymorphism (G/T), 46 homozygous for the T allele, and 16 were homozygous for the G-allele. Real-time RT-PCR measurements of FDH mRNA did not indicate a significant difference in transcript levels between the heterozygous and the homozygous groups. The in vitro comet assay after FA exposure of blood samples obtained from 5 homozygous GG and 3 homozygous TT subjects did not lead to a significant difference between these two groups. Altogether, our study did not identify biologically relevant polymorphisms in transcribed regions of the FDH gene, which may lead to inter-individual differences in the metabolic inactivation of FA.
authors.affiliation: Universität Ulm, Institut für Humangenetik, Ulm, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Just
authors.forename: Jasmin
authors.initials: J
authors.lastname: Zeller
authors.forename: Clarissa
authors.initials: C
authors.lastname: Riegert
authors.forename: Günter
authors.initials: G
authors.lastname: Speit
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000445:Aldehyde Oxidoreductases / Q000235:genetics*; D000483:Alleles; D020552:Comet Assay; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: C020145:formaldehyde dehydrogenase (glutathione); D000445:Aldehyde Oxidoreductases