title: Association of A(313)G glutathione S-transferase P1 germline polymorphism with susceptibility to de novo myelodysplastic syndrome.
abstract: Models for the pathogenesis of myelodysplastic syndrome (MDS) imply the role of individual genetic variations in genes involved in detoxification mechanisms. GSTP1 enzyme plays a key role in the biotransformation of a variety of carcinogens. The corresponding gene is subject to a single nucleotide polymorphism (A(313)G) leading to abolished enzyme activity. In order to evaluate whether the GSTP1 polymorphism influences MDS susceptibility, we conducted a case-control study comprising 310 de novo patients and 370 healthy controls using a real-time polymerase chain reaction (PCR) genotyping method. The GSTP1 gene status was also evaluated in relation to patients' characteristics and chromosomal abnormalities. A significantly higher incidence of the GSTP1 variant genotypes was observed in patients with MDS compared to controls (p < 0.0001). The results revealed increased frequencies of heterozygotes in patients younger than 60 years old and of homozygotes G/G in older patients (p = 0.007). Our results provide evidence for a pathogenetic role of the GSTP1 polymorphism in MDS risk, probably in an age-dependent manner.
authors.affiliation: Laboratory of Health Physics and Environmental Health , NCSR "Demokritos", Athens, Greece.
authors.forename: Sophia
authors.initials: S
authors.lastname: Zachaki
authors.forename: Chrysa
authors.initials: C
authors.lastname: Stavropoulou
authors.forename: Marina
authors.initials: M
authors.lastname: Kalomoiraki
authors.forename: Theodora
authors.initials: T
authors.lastname: Koromila
authors.forename: Aggeliki
authors.initials: A
authors.lastname: Daraki
authors.forename: Kalliopi N
authors.initials: KN
authors.lastname: Manola
authors.forename: Ariadni
authors.initials: A
authors.lastname: Mavrou
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Kanavakis
authors.forename: Gabriel E
authors.initials: GE
authors.lastname: Pantelias
authors.forename: Constantina
authors.initials: C
authors.lastname: Sambani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D002869:Chromosome Aberrations; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D051549:Glutathione S-Transferase pi