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The Role Of Multidrug Resistance Gene 1 Polymorphism To Prognosis Of Adult Acute Lymphoblastic Leukemia Patients

Posted on:2009-01-22Degree:MasterType:Thesis
Country:ChinaCandidate:R R LiuFull Text:PDF
GTID:2144360245482117Subject:Hematology
Abstract/Summary:PDF Full Text Request
Objective:This study investigated the relation between the three most frequent Single nucleotide polymorphisms(SNPs)of MDR1 gene: G2677A/T,C1236T and C3435T,and the risk of adult ALL patients' therapeutic effect and prognosis,in order to investigate the possible molecular mechanism of poor therapeutic effect and prognosis of adult ALL patients and provide the theory basis to improve the therapeutic effect and prognosis of adult ALL patients.Methods:1)Genomic DNAs were isolated from EDTA- anticoagulated whole blood cells.Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)method was used for genotyping.2)Compare the frequencies of 3435T,1236T,2677T,2677A between the ALL group and the healthy group byχ~2 test.3)Dividing all patients into two groups:refractoriness group and refractoriness-free group,compare the frequencies of C3435T,C1236T,G2677T/A between the two groups byχ~2 test.4)Compare the DFS(disease-free survival)and OS(Overall survival)in one year follow-up period between the three SNPs wide groups and non-wide groups byχ~2 test.Results:(1)Among 48 cases,the frequencies of C/T alleles in site 3435 are 0.479/0.521;the frequencies of C/T alleles in site 1236 are 0.271/0.729;the frequencies of G/T/A alleles in site 2677 are 0.719, 0.024 and 0.041.Among 100 healthy cases,the frequencies of C/T allelic in site 3435 are 0.66/0.34;the frequencies of C/T allelic in site 1236 are 0.653/0.347;the frequency of G/T/A allelic in site 2677 are 0.775,0.098 and 0.127.All of genotypes consistent with Hardy-weinberg law(P>0.05).The difference of C3435T,C1236T,G2677T/A gene frequency distributions between ALL group and healthy group is of statistical significance(P<0.05)(2)The difference of C3435T,C1236T, G2677T/A gene frequency distributions between refractory group and refractory-free group has no statistical significance(P>0.05);Between refractory and refractory-free patients,there was no significant diference in the distribution of allelic frequency of MDR1 C1236T,G2677A, C3435T(P>0.05).We took TT,TG or AT(carrying at least one variant T allele)as 2677T carrier group and AA,GA or GG as 2677T noncarrier one.The association between refractory and 2677T carrier was significant (P<0.05),elimimating other clinical parameters' influence,for example:age,gender.(3)By Follow-Up ended,17 patients died of the recurrence,27 patients were still alive by chemotheraphy after recurrence,and 4 patients were alive without recurrence.Among 39 2677T carriers,2 patients were alive without recurrence,and 3 in 9 2677T noncarriers.The corresponding 1-year OS rates were 60%and 75%and the 1-year EFS rates were 7.5%and 25%,respectively.There were no significant diferences in EFS rate and in OS rate(P>0.05). Conclusions:(1)Frequency of MDR1 polymorphism C1236T, G2677A,G2677T and C3435T in adult ALL patients was signifycantly higher than the healthy population.(2)MDR1 polymorphism 2677T carrier genotype were one of the risk factors for predicting refractoriness to adult ALL patients.(3)Between refractory and refractory-free patients, there was no significant diferences in distribution of allelic frequency of MDR1 polymorphism C1236T,G2677A and C3435T.(4)There was no significant association between 2677T carrier or not and DFS,OS in 1 year.G2677T carrier or not maybe had no difference with the prognosis to adult ALL patients.
Keywords/Search Tags:Multidrug Resistance Gene 1, Gene Polymorphism, Acute Lymphocytic Leukemia
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