Bahrehmand Fariborz, Kiani Amir, Vaisi-Raygani Asad, Bashiri Homayoun, Zobeiri Mehdi, Moini Ali, Pourmotabbed Tayebeh
Fertility and Infertility Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. AND Department of Clinical Biochemistry, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Regenerative Medicine Research Center, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Acta Med Iran. 2017 Jun;55(6):360-367.
Thiopurine drugs remain pivotal therapies for the wide varieties of diseases such as inflammatory bowel disease (IBD). Here, thiopurine S-methyltransferase (TPMT) phenotype, the main metabolizing enzyme of thiopurine-drugs, was studied. This is for the first time that TPMT activity is measured in Iranian IBD patients. We used an improved direct liquid chromatography assay without need for solvent extraction and minimize excess labor handling making it ideal for use in routine referral medical centers. TPMT activity in whole blood was determined by a non-extraction HPLC method. We evaluated 427 individuals including 215 IBD patients and 212 unrelated healthy individuals as control group from Iran's western population. TPMT phenotyping of this study demonstrated no frequency for deficient, 2.8 % for low and 97.2% for normal activity, which is different with results of other studies. There was a significant negative correlation between TPMT activities as calculated based on nmol/grHb/h and the Hb-levels in IBD and control groups (r= -0.54, P<0.001 and r= -0.27, P<0.001), respectively. Interestingly a significant positive correlation between Hb levels and TPMT-activities were seen when the activity calculated in mU/L in IBD patients and control subjects (r=0.14, P=0.05 and r=0.43, P<0.001), respectively. We strongly suggest the use of international unit (mU/L) is more appropriate than nmol6MTG/grHb/h for expressing TPMT-activity in IBD patients. In addition, in comparison with other providers of TPMT test activity and centers around the world the risk of toxicity is much lower after utilizing thiopurine drugs for IBD patients in this region.
硫嘌呤类药物仍然是治疗多种疾病（如炎症性肠病（IBD））的关键疗法。在此，我们研究了硫嘌呤类药物的主要代谢酶硫嘌呤甲基转移酶（TPMT）的表型。这是首次在伊朗IBD患者中测量TPMT活性。我们使用了一种改进的直接液相色谱法，无需溶剂萃取，减少了多余的手工操作，使其非常适合在常规转诊医疗中心使用。全血中的TPMT活性通过非萃取高效液相色谱法测定。我们评估了427名个体，其中包括215名IBD患者和212名来自伊朗西部人群的无关健康个体作为对照组。本研究的TPMT表型分析显示，缺乏活性的频率为零，低活性的频率为2.8%，正常活性的频率为97.2%，这与其他研究结果不同。在IBD组和对照组中，基于nmol/grHb/h计算的TPMT活性与血红蛋白水平之间分别存在显著负相关（r = -0.54，P < 0.001和r = -0.27，P < 0.001）。有趣的是，当以mU/L计算IBD患者和对照组的活性时，血红蛋白水平与TPMT活性之间分别存在显著正相关（r = 0.14，P = 0.05和r = 0.43，P < 0.001）。我们强烈建议，对于IBD患者，使用国际单位（mU/L）比nmol6MTG/grHb/h更适合表达TPMT活性。此外，与世界其他提供TPMT检测活性的机构和中心相比，该地区IBD患者使用硫嘌呤类药物后毒性风险要低得多。
