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Correlation Study On Nrf2,NQO1,HO1 Gene Polymorphisms And GVHD After Allogeneic Hematopoietic Stem Cell Transplantation

Posted on:2017-06-15Degree:MasterType:Thesis
Country:ChinaCandidate:M LiuFull Text:PDF
GTID:2334330503990665Subject:Blood disease
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Objective To detect the gene sequence of Nrf2,NQO1 and HO1 of recipients and donors underwent allogeneic hematopoietic stem cell transplantation(allo-HSCT),then to further explore the correlation between these gene polymorphisms and GVHD.Methods We collected peripheral blood samples from 70 couples of recipients and donors underwent allo-HSCT from February 2015 to January 2016.Then we detected the parts of DNA sequence of Nrf2(-617G/T,-650 C/A,-651 C/ T,-653 C/T,-684 C/T,-686 A/G),NQO1(-609C/T)and HO1(-413A/T).We alss observed the clinical manifestations of GVHD after allo-HSCT. Follow-up time was 3 to14 months, with a median time of 7 months. We analyzed the relationship between GVHD and these gene polymorphysms described above.Results(1)In 70 patients, 7 patients died less than 3 months after allo-HSCT, only 63 cases were performed for statistical analysis. 44 patients did not suffer acute graft-versus-host disease(a GVHD).19 patients suffered a GVHD,in which 8 patients had?degree a GVHD,11 cases occurred with?to?degree a GVHD.4 cases of patients presented with chronic graft-versus-host disease(c GVHD),of two werelimited,two were extensive.(2)Three genotypes(GG,GT,TT) were detected in Nrf2-617G/T, three genotypes(CC,CT,TT) were detected in Nrf2-651C/T, three genotypes(CC,CT,TT) were detected in Nrf2-653C/T. The occurrences of a GVHD and ?to?degree a GVHD were not significantly different between frequencies of these genotypes and alleles of the donors and recipients. One genotype(CC) was detected in-650C/A, one genotype(TT) was detected in-684C/T, one genotype(AA) was detected in-686A/G, with no statistical analysis.(3) Three genotypes(CC,CT,TT) were detected in NQO1-609C/T. The occurrences of a GVHD and ?to?degree a GVHD were not significantly different between frequencies of these genotypes and alleles of the donors and recipients.(4) Three genotypes(AA,AT,TT) were detected in HO1-413A/T.Genotypes and alleles in 19 a GVHD patients were 2(10.5%),8(42.1%) and 9(47.4%),with no significant difference(P=0.111). The a GVHD patients with allele T and allele A were 26(68.4%) and 12(31.6%),the incidence rate of a GVHD was significantly higher with allele T(P=0.033). AA genotype was not detected in 11 cases of ?to ? degree a GVHD,AT genotype was 6(54.5%) and TT genotype was 5(45.5%),these genotypes were significantly different(P=0.039).The frequencies of allele T and allele A were 16(72.7%) and 6(27.3%).The incidence rate of ?to ? a GVHD with T allele was increased but without statistical significance(P = 0.052). The occurrences of a GVHD and ? to ? degree a GVHD were not significantly different between frequencies of these genotypes and alleles of the donors.(5) 4 cases of patients presented with c GVHD,with no statistical analysis.Genotypes of Nrf2(-617G/T) were GG 1(25%),GT 2(50%) and TT 1(25%).Genotypes of Nrf2(-651C/T) were CC 3(75%) and CT 1(25%).Genotypes of Nrf2(-653 C/T) were CT 3(75%) and TT 1(25%).Genotypes of NQO1(-609C/T) were CT 2(50%) and TT 2(50%). Genotypes of HO1(-413A/T) were AA 1(25%),AT 1(25%) and TT 2(50%).Conclusion The polymorphisms of Nrf2(-617G/T,-651C/T,-653C/T) and NQO1(-609C/T) in donors and recipients may not contribute to the development of a GVHDafter allo-HSCT,as well as the polymorphism of HO1(-413A/T) in donors.The polymorphism of HO1(-413A/T) in recipients was related to the occurrence of a GVHD.The incidence rate of a GVHD was significantly higher with allele T.The occurrence rate of ?to ? degree a GVHD may increase but without statistical significance with allele T. The further studies are needed to explore the correlation between GVHD and gene polyomrphisms.
Keywords/Search Tags:Nrf2, NQO1, HO1, polymorphism, GVHD
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