ATM gene single nucleotide polymorphisms predict regimen-related gastrointestinal toxicity in patients allografted after reduced conditioning
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
25759145
DOI
10.1016/j.bbmt.2015.02.021
PII: S1083-8791(15)00151-2
Knihovny.cz E-zdroje
- Klíčová slova
- ATM gene, Acute graft-versus-host disease, Allogeneic hematopoietic stem cell transplantation, Gastrointestinal toxicity, Single-nucleotide polymorphism,
- MeSH
- akutní nemoc MeSH
- alely MeSH
- analýza přežití MeSH
- ATM protein genetika imunologie MeSH
- dárci tkání MeSH
- dospělí MeSH
- exprese genu MeSH
- frekvence genu MeSH
- gastrointestinální trakt účinky léků imunologie patologie MeSH
- haplotypy MeSH
- hematologické nádory genetika imunologie mortalita terapie MeSH
- homologní transplantace MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé středního věku MeSH
- lidé MeSH
- myeloablativní agonisté aplikace a dávkování škodlivé účinky MeSH
- nemoc štěpu proti hostiteli genetika imunologie mortalita MeSH
- příprava pacienta k transplantaci metody MeSH
- prognóza MeSH
- prospektivní studie MeSH
- protein - isoformy genetika imunologie MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ATM protein, human MeSH Prohlížeč
- ATM protein MeSH
- myeloablativní agonisté MeSH
- protein - isoformy MeSH
Polymorphisms of genes involved in innate and adaptive immunity have become an object of major interest in regard to hematopoietic stem cell transplantation (HSCT) complications. Regimen-related gastrointestinal toxicity (RR-GIT) is the dominant complication during the pre-engraftment period and has been linked to increased risk of graft-versus-host disease (GVHD) development. According to our hypothesis, functional variants of genes participating in DNA damage response (DDR) may have an impact on the extent of tissue damage caused by the conditioning regimen. In our single-center study, we analyzed 62 patients who underwent HSCT from HLA-identical donors after reduced conditioning. The patients were genotyped for 5 single nucleotide polymorphisms (SNPs, rs4585 T/G, rs189037 A/G, rs227092 T/G, rs228590 C/T, and rs664677 T/C) of the ATM gene-the essential member of the DDR pathways, using allele-specific matrix-assisted laser desorption/ionization, time-of-flight (MALDI-TOF) mass spectrometry assay. Because of almost absolute linkage disequilibrium observed among all 5 SNPs, association of 2 major ATM haplotypes (ATM1/ATM2) with RR-GIT and acute GVHD (aGVHD) was analyzed. Importantly, the univariate and multivariate analysis showed that patients homozygous for ATM2 haplotype (rs4585*T, rs189037*A, rs227092*T, rs228590*C, and rs664677*T) are more likely to suffer from high-grade RR-GIT than ATM1 homozygous patients. The association with aGVHD was not significant. To our knowledge, this is the first report showing the ATM gene variability in relation to RR-GIT in the allogeneic HSCT setting.
