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The TPMT Genetic Polymorphism and Activity Detection in the Treatment of Ulcerative Colitis

Author: DuanLiJuan
Tutor: ZuoYingLei; DuanLiPing
Course: Internal Medicine
Keywords: ulcerative colitis thiopurine methyltransferase gene polymorphism activity efficacy adverse drug reaction azathiopurine
CLC: R574.1
Type: Master's thesis
Year: 2012
Downloads: 47
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Objcetive:To predict the efficacy and side effects of AZA in treating patients with ulcerative colitis by studying TPMT gene polymorphism in Yunnan Province.Methods:40patients with ulcerative colitis and30healthy were divided into two groups, during July2010to August2011in1st affiliated hospital of Kunming Medical University.TPMT genotypes were determined. Allele-specific PCR (ASPCR) and PCR-restriction fragment length polymorphism (RFLP) were used to test the frequency of TPMT*2(G238C)、 TPMT*3C(A719G)、TPMT*3B(G460A) and TPMT*3A(G460A&A719G), respectively. To observe the efficacy and safety in9patients who took azathioprine as their treatment against ulcerative colitis.Resluts:①TPMT*2, TPMT*3A and TPMT*3B were not detected in both two groups, and only4TPMT*3C heterozygotes were identified. The frequency of TPMT mutant alleles was3.3%(2/60) in healthy group, which of was2.5%(2/80) in UC group. However, the difference was not statistically significant(p>0.05).②In9patients took AZA,2had TPMT*3C heterozygous mutation and those patients experienced bone marrow during the treatment. TPMT mutations alleles were not detected in any of the5patients without side effects and2patients suffered other side effects.Conclusion:①TPMT*3C appears to be the most prevalent among the known mutant TPMT allele in Yunnan people, both the healthy and UC patients. TPMT*2、 TPMT*3A and TPMT*3B were not detected in those people. The frequency of the Objective:In this part, to explore relations between TPMT activity and TPMT gene polymorphism in Yunnan region and predict the efficacy and adverse effects in ulccrative colitis patients who take azathioprinc (AZA).Methods:TPMT activity was detected with high performance liquid chromatography (HPLC) in40UC patients and30healthy individuals. To research9UC patients taking azathioprine on their drug efficacy and safety.Resluts:①In the40patients, TPMT activity ranged from3.07to16.05U/ml pRBC (mean7.01±2.77U/ml pRBC). TPMT activity ranged from3.78to19.57U/ml pRBC (mean6.98±3.01U/ml pRBC) in the healthy group. However, the difference was not statistically significant (p>0.05).②TPMT activity and genotype were significantly correlated (p<0.05). correlation coefficient. Kendall’s r-0.329. In addition, TPMT activity and genotype test results corresponded at95.7%and the specificity that TPMT gene mutations predicting low TPMT activity reached100%.③1of the9patients terminated treatment due to severe side effect, the rest all had taken AZA for more than6months. In the9patients,2had TPMT*3C heterozygous mutation, their TPMT activity were lower than5.0U/mlpRBC and those patients experienced bone marrow during AZA treatment. No hepatotoxicity was found. Another2patients with other drug adverse reactions and their TPMT activity were similar to those who didn’t have any side effects, but the difference was not known mutant TPMT alleles is low, which suggests that zazthioprine treating UC patients is safe and effective in Yunnan.②TPMT gene mutations have a high specificity on predicting AZA bone marrow, but not all of the AZA side effects can be explained with TPMT gene polymorphism. TPMT gene polymorphism can partly predict adverse effects in UC patients taking AZA and provide reference on treatment dose. statistically signifieant (p>0.05).④8UC patients received AZA therapy more than6months,87.5%achieved remission and12.5%failed. Patients who did not achieved remission had a TPMT activity (15.89U/mlpRBC) higher than14.0U/mlpRBC.Conclusion:①TPMT activity and genotypes were significantly related, both the results of detection were at high correspondence. TPMT gene mutations have a high specificity on predicting low TPMT activity, but low TPMT activity can not be completely explained with genetic mutations.②Patients with low TPMT activity have a higher risk of bone marrow taking AZA.③TPMT activity and efficacy of AZA may be related, the detection of TPMT activity can well predict the efficacy and side effects taking AZA in patients with ulcerative colitis and help to decide option treatment dose.

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CLC: > Medicine, health > Internal Medicine > Digestive and abdominal diseases > Bowel disease > Ulcer
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