کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2101564 1546266 2015 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
ATM Gene Single Nucleotide Polymorphisms Predict Regimen-Related Gastrointestinal Toxicity in Patients Allografted after Reduced Conditioning
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
ATM Gene Single Nucleotide Polymorphisms Predict Regimen-Related Gastrointestinal Toxicity in Patients Allografted after Reduced Conditioning
چکیده انگلیسی


• ATM senses DNA damage and regulates DNA-damage response.
• Five ATM gene variants (single nucleotide polymorphisms) were associated with severe conditioning-induced gastrointestinal toxicity.
• ATM gene variants may influence the extent of conditioning-induced tissue damage.
• ATM gene pretransplantation analysis may be helpful in tailoring the patient's therapy.

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 21, Issue 6, June 2015, Pages 1136–1140
نویسندگان
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