| Objective:To investigate the genotype distribution of TET2(rs2454206,rs12498609)and ASXL1(rs3746609)single nucleotide polymorphisms(SNPs)in patients with myelodysplastic syndrome(MDS)and the relation between these SNPs and the risk of myelodysplastic syndrome(MDS).To determine if there is association between TET2(rs2454206,rs12498609),ASXL1(rs3746609)and the clinical features,gene mutation status in patients with myelodysplastic syndrome(MDS).To compare the overall survival rate and disease progression rate of patients with different genotypes of these three SNPs,in order to clarify the relationship between TET2(rs2454206,rs12498609)and ASXL1(rs3746609)polymorphisms and the clinical prognosis of patients with MDS.Methods:1.The genotype distribution of TET2(rs2454206,rs12498609)and ASXL1(rs3746609)single nucleotide polymorphisms and their relationship with risk of MDSBone marrow samples from 90 patients with MDS were collected at diagnosis and peripheral blood samples from 143 healthy volunteers were collected.Then DNA was extracted from these samples,and primers were designed for PCR.Then genotyping every case by polymerase chain reaction(PCR)and direct sequencing.The genotype distribution of deferent genotype of these polymorphisms was compared between the MDS group andthe healthy control group.2.Clinical features in patients with MDS with different genotypes of TET2(rs2454206,rs12498609)and ASXL1(rs3746609).To collect the clinical and laboratory index of MDS patients,including clinical information such as age,sex;laboratory index such as peripheral blood leukocyte count,hemoglobin concentration,platelet count,neutrophil count,lactate dehydrogenase(LDH),T lymphocyte subsets,proportion of bone marrow blast cells,karyotype analysis and gene mutation status.These features of MDS patients with different genotype of the SNPs were statistically described and compared.3.Overall survival and disease progression of MDS patients with different genotypes of TET2(rs2454206,rs12498609)and ASXL1(rs3746609).Follow-up was carried out through medical records and telephone follow-up.The total survival(OS)stage was defined as the time from diagnosis to death or the last follow-up.Disease progression was referred to the transformation from MDS to AML.The overall survival rate and disease progression rate were compared between the two groups.Results:1.In 90 patients with MDS,the frequency of TET2 rs2454206 allele A was 93.3%,the frequency of G was 6.7%;the frequency of TET2 rs12498609 allele C was 94.4%,the frequency of G was 5.6%.The frequency of ASXL1 rs3746609 allele G was 94.9% and that of A was 5.1%.In the healthy control group,the frequency of TET2 rs2454206 allele A and G were 75.5%,25.5%respectively.The frequency of allele C and G of TET2rs12498609 were 87.8% and 12.2%.And the frequency of ASXL1 rs3746609 alleles G and A were 86.4% and 13.6%.There was no significant difference in age(P = 0.076)and sex(P = 0.263)between the patients and the healthy control group.There was significant difference in the allele frequency between the patients and the healthy control group(P <0.001,P =0.017,P = 0.003).The genotype distribution of each point in the control group obeyed the law of Hardy-Weinberg genetic balance(P = 0.69,P = 0.999,P =0.54).2.In MDS,the level of LDH in peripheral blood of patients with TET2 rs2454206G/A genotype was higher than those with A/A genotype(P=0.025),and the patients with TET2 rs12498609 G/C had lower rate of anemia(P =0.026)and higher mutation rate of SRSF2 gene(P=0.042)than those with type C/C.ASXL1rs3746609 A/G type was found to be related to higher platelet count(P =0.02),higher total T cell proportion(P=0.029)and lower proportion of NK and B cells.There was no significant difference in other indexes among patients with different genotypes of TET2(rs2454206,rs12498609)and ASXL1(rs3746609).3.There was no significant difference in overall survival rate between MDS patients with different genotypes of TET2(rs2454206,rs12498609)and ASXL1(rs3746609)(P=0.691,P=0.203,P=0.310).A total of 14 of 90 patients were observed to turn out to AML,but there was no significant difference in conversion rate between genotypes of the three SNP genotypes(P =1.0,P =0.95,P =0.377).Conclusions:1.The frequency of TET2 rs2454206 A,TET2 rs12498609 C and ASXL1 rs3746609 G in MDS patients was significantly higher than that in normal controls,which was a risk factor for MDS.2.TET2 rs2454206 was related to the level of serum LDH in patients with MDS,TET2 rs12498609 was related to anemia and SRSF2 gene mutation in MDS patients,ASXL1 rs3746609 was related to peripheral blood platelet count and the proportion of immune system subsets in MDS patients.3.All the three SNP loci were not associated with the prognosis and transformation to AML in patients with MDS. |
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