hrm技术在炎症性肠病患者tpmt基因多态性的检测中的应用性研究临床医学专业论文.docxVIP

Application Application Research of HRM Technology in Detection of TPMT Gene Polymorphism in Inflammatory Bowel Disease Patients Abstract Background：Azathioprine(AZA)iS a common drug which iS used to treat inflammatory bowel disease(IBD)，however it may cause the myelotoxicity in some patients．Recent studies indicated that the drug adverse reaction had some relationship with the mutation of thiopurine methyltransferase (TPMT)． Objective To diSCUSS the relationship between the genotype of TPMT and AZA induced myelotoxicity in the patients wi th IBD．Methods Peripheral blood was collected from 82 IBD patients and 53 healthy Chinese people． Genomic DNA was isolated from these blood samples with a QIAamp DNA Blood Mini Kit(Qiagen)，and three commom mutation alleles of TPMT [TPMT*3A(G460A／A719G)，TPMT*3B(G460A)，TPMT*3C(ATl9G)]were detected by polymerase chain reaction—high resolution melting and sequencing．Result elinical data：There were 82 IBD patients(UC 38／CD 42／IC 2)，who were divided into group A and B based on whether they used AZA or not．Group A was composed by 31 patients who received AZA(50一lOOmg／d)(male 20／female 1 1)whose average age was 39．6(18—68)years old．The healthy control group was group C(mal e28／femal e 25)，average age 4 1．05(23—68)．There was no significant difference between the age of either group A and C or group B and C．Six cases of heterozygote TPMT*1／．3C were detected，which accounted for 4．44％of the test population．Four cases of heterozygote TPMT*I／．3C were found in IBD patients，making genotypic frequency of the heterozygote TPMT*I／*3C 4．88％，and mutation allele frequency in these patients 2．44％． While two cases of heterozygote TPMT*I／*3C were found in healthy people， SO genotypic frequency of the heterozygote TPMT*I／*3C was3．77％．Mutation allele frequency in these people was 1．89％．No TPMT*3A or TPMT*3B was found． Bone marrow suppression occurred in four of the patients who received AZA， but only one of them has the TPMT*I／*3C mutation，the others