Linked Life Data

10975610

Source:http://linkedlifedata.com/resource/pubmed/id/10975610

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pubmed-article:10975610pubmed:abstractTextGlutathione S-transferase theta enzyme activity involved in the metabolism of toxic compounds is absent in approximately 20% of Caucasians due to a homozygous deletion of GSTT1 (*0/0). Because the exact manner of the GSTT1 deletion was unknown, current genotyping of GSTT1 was limited to detect the presence versus complete absence of the gene by a GSTT1-specific polymerase chain reaction (PCR). Thus, heterozygous (*A/0) and homozygous (*A/A) samples could not be discriminated. We have characterized the boundaries of the deletion of the human glutathione S-transferase theta (GSTT1) gene: PCR mapping and sequencing revealed a 54251 bp fragment including GSTT1 to be deleted from chromosome 22, most likely by a homologous recombination event between two highly homologous sequence stretches that flank GSTT1. Based on the knowledge of the GSTT1*0 region, a PCR assay was devised for unambiguous discrimination of homozygously deleted (*0/0), heterozygously (*A/0) and homozygously GSTT1 carrying (*A/A) individuals. Genotyping of 180 samples of a Caucasian population revealed that the deletion consists of one defined allele, whose distribution in the population fits the Hardy-Weinberg equilibrium with observed 20% *0/0, 46% *A/0 and 34% *A/A individuals. The number of GSTT1*A alleles detected by this procedure correlated highly significant with the enzyme activity in erythrocytes. Genotype-phenotype comparisons demonstrated a codominant type of inheritance by a gene-dose effect: samples with two active alleles expressed a statistically significant higher enzymatic activity compared to those with one null allele (P < 0.0001, ANOVA).lld:pubmed
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pubmed-article:10975610pubmed:volume10lld:pubmed
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pubmed-article:10975610pubmed:pagination557-65lld:pubmed
pubmed-article:10975610pubmed:dateRevised2006-11-15lld:pubmed
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pubmed-article:10975610pubmed:articleTitleCharacterization of the glutathione S-transferase GSTT1 deletion: discrimination of all genotypes by polymerase chain reaction indicates a trimodular genotype-phenotype correlation.lld:pubmed
pubmed-article:10975610pubmed:affiliationEpidauros Biotechnology, Pharmacogenetics Laboratory, Bernried, Germany.lld:pubmed
pubmed-article:10975610pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:10975610pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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