Abstract：
OBJECTIVE: Thiopurine-related leukopenia is associated with polymorphisms in the thiopurine methyltransferase (TPMT) and nucleoside diphosphate-linked moiety X type motif 15 (NUDT15) genes. However, those polymorphisms explain only a fraction of thiopurine-related leukopenia. Our aim was to study the role of an inosine triphosphate pyrophosphatase (ITPA) polymorphism in patients with inflammatory bowel disease (IBD) and thiopurine-related leukopenia that was unexplained by the TPMT and NUDT15 polymorphisms.
METHODS: We enrolled consecutive IBD patients on thiopurines (azathioprine or 6-mercaptopurine) from January 2019-March 2020, at a tertiary care center in North India. The presence of the ITPA (C.94C > A) polymorphism was evaluated in all patients, along with its association with thiopurine-related leukopenia.
RESULTS: Of the 33 patients (from a total of 119 patients) that developed leukopenia, 8 had the TPMT (n = 1) or NUDT15 (n = 7) polymorphism. Of the remaining 111 patients, their mean age was 36.36 ± 13.54 years and 57 (51.3%) were males. Twenty-five (21.01%) had unexplained leukopenia. The ITPA polymorphism was detected in 4 (16%) patients in the unexplained leukopenia group and 24 (27.9%) patients in the non-leukopenia group (p = 0.228). The odds ratio for predicting leukopenia with the ITPA polymorphism was 0.4921 (95% CI 0.1520-1.5830, p = 0.234).
CONCLUSIONS: The ITPA (C.94C > A) polymorphism was frequently detected in the study population but was not predictive for leukopenia in patients with IBD on thiopurine therapy.
METHODS: We enrolled consecutive IBD patients on thiopurines (azathioprine or 6-mercaptopurine) from January 2019-March 2020, at a tertiary care center in North India. The presence of the ITPA (C.94C > A) polymorphism was evaluated in all patients, along with its association with thiopurine-related leukopenia.
RESULTS: Of the 33 patients (from a total of 119 patients) that developed leukopenia, 8 had the TPMT (n = 1) or NUDT15 (n = 7) polymorphism. Of the remaining 111 patients, their mean age was 36.36 ± 13.54 years and 57 (51.3%) were males. Twenty-five (21.01%) had unexplained leukopenia. The ITPA polymorphism was detected in 4 (16%) patients in the unexplained leukopenia group and 24 (27.9%) patients in the non-leukopenia group (p = 0.228). The odds ratio for predicting leukopenia with the ITPA polymorphism was 0.4921 (95% CI 0.1520-1.5830, p = 0.234).
CONCLUSIONS: The ITPA (C.94C > A) polymorphism was frequently detected in the study population but was not predictive for leukopenia in patients with IBD on thiopurine therapy.
摘要：
目的：硫嘌呤相关性白细胞减少症与硫嘌呤甲基转移酶（TPMT）和核苷二磷酸连接部分X型基序15（NUDT15）基因的多态性有关。然而,这些多态性仅解释了一部分与硫嘌呤相关的白细胞减少症。我们的目的是研究三磷酸肌苷焦磷酸酶（ITPA）多态性在炎症性肠病（IBD）和硫嘌呤相关白细胞减少症患者中的作用，而TPMT和NUDT15多态性无法解释。
方法：我们从2019年1月至2020年3月在印度北部的三级护理中心招募了连续的IBD患者接受硫嘌呤（硫唑嘌呤或6-巯基嘌呤）治疗。在所有患者中评估ITPA（C.94C>A）多态性的存在，以及它与硫嘌呤相关的白细胞减少症的关系。
结果：在发生白细胞减少症的33例患者（共119例患者）中，8具有TPMT(n=1)或NUDT15(n=7)多态性。在剩下的111名患者中,他们的平均年龄为36.36±13.54岁，男性为57岁（51.3％）。25例（21.01％）患有无法解释的白细胞减少症。在无法解释的白细胞减少症组的4例（16％）患者和非白细胞减少症组的24例（27.9％）患者中检测到ITPA多态性（p=0.228）。ITPA多态性预测白细胞减少的比值比为0.4921（95％CI0.1520-1.5830，p=0.234）。
结论：在研究人群中经常检测到ITPA（C.94C>A）多态性，但不能预测接受噻嘌呤治疗的IBD患者的白细胞减少。
方法：我们从2019年1月至2020年3月在印度北部的三级护理中心招募了连续的IBD患者接受硫嘌呤（硫唑嘌呤或6-巯基嘌呤）治疗。在所有患者中评估ITPA（C.94C>A）多态性的存在，以及它与硫嘌呤相关的白细胞减少症的关系。
结果：在发生白细胞减少症的33例患者（共119例患者）中，8具有TPMT(n=1)或NUDT15(n=7)多态性。在剩下的111名患者中,他们的平均年龄为36.36±13.54岁，男性为57岁（51.3％）。25例（21.01％）患有无法解释的白细胞减少症。在无法解释的白细胞减少症组的4例（16％）患者和非白细胞减少症组的24例（27.9％）患者中检测到ITPA多态性（p=0.228）。ITPA多态性预测白细胞减少的比值比为0.4921（95％CI0.1520-1.5830，p=0.234）。
结论：在研究人群中经常检测到ITPA（C.94C>A）多态性，但不能预测接受噻嘌呤治疗的IBD患者的白细胞减少。
