Polymorphisms in thiopurine methyltransferase (TPMT) and Nudix hydrolase-15 (NUDT15) have been implicated as the predominant cause of thiopurine induced leukopenia in the Western countries and East Asia respectively. Exact role of these polymorphisms in South Asian population with inflammatory bowel disease (IBD) is uncertain. We included consecutive patients with IBD who were initiated on thiopurines at a center in North India. The dosage of thiopurines was titrated using regular monitoring of hemogram and liver function tests. Three TPMT polymorphisms (c.238 G > C, c.460 G > A, and c.719A > G) and one NUDT15 polymorphism (c.415 C > T) were assessed. Comparison regarding incidence of leukopenia and maximum tolerated thiopurine dosage was performed between those with wild polymorphism and those with TPMT and NUDT15 polymorphisms, respectively. Of the 119 patients (61 males, mean age 36.8 ± 13.5 years), 105 (88.2%) had ulcerative colitis and 14 (11.8%) had Crohn’s disease. Leukopenia was noted in 33 (27.7%), gastrointestinal intolerance in 5 (4.2%) and pancreatitis in 2 (1.6%). TPMT polymorphisms were detected amongst five patients of whom 1 developed leukopenia. NUDT15 polymorphism was noted in 13 patients of whom 7 had leukopenia. The odds of developing leukopenia in TPMT polymorphism were non-significant (0.77, 95% CI:0.0822 to 7.2134, P = 0.819) but were significantly higher in those with NUDT15 polymorphism (3.5933, 1.1041 to 11.6951, P value: = 0.0336). NUDT15 polymorphism was more frequent than TPMT polymorphisms and was associated with thiopurine induced leukopenia. However, the tested polymorphisms account for only 24.2% of the risk of thiopurine induced leukopenia.

中文翻译：

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硫嘌呤诱导的炎症性肠病白细胞减少症中的 TPMT 和 NUDT15 多态性：来自印度的一项前瞻性研究


硫嘌呤甲基转移酶 (TPMT) 和 Nudix 水解酶-15 (NUDT15) 的多态性分别被认为是西方国家和东亚国家硫嘌呤诱导的白细胞减少症的主要原因。这些多态性在南亚炎症性肠病 (IBD) 人群中的确切作用尚不确定。我们纳入了在印度北部的一个中心开始服用硫嘌呤的连续 IBD 患者。通过定期监测血象和肝功能测试来滴定硫嘌呤的剂量。评估了三种 TPMT 多态性（c.238 G > C、c.460 G > A 和 c.719A >G）和一种 NUDT15 多态性（c.415 C > T）。分别对野生型多态性与TPMT和NUDT15多态性的白细胞减少症发生率和最大耐受硫嘌呤剂量进行比较。在 119 名患者（61 名男性，平均年龄 36.8 ± 13.5 岁）中，105 名（88.2%）患有溃疡性结肠炎，14 名（11.8%）患有克罗恩病。 33 例 (27.7%) 出现白细胞减少症，5 例 (4.2%) 出现胃肠道不耐受，2 例 (1.6%) 出现胰腺炎。在 5 名患者中检测到 TPMT 多态性，其中 1 名患者出现白细胞减少症。在 13 名患者中发现了 NUDT15 多态性，其中 7 名患者患有白细胞减少症。 TPMT 多态性患者发生白细胞减少症的几率不显着（0.77，95% CI：0.0822 至 7.2134，P = 0.819），但 NUDT15 多态性患者发生白细胞减少症的几率显着较高（3.5933，1.1041 至 11.6951，P 值：= 0.0336）。 NUDT15 多态性比 TPMT 多态性更常见，并且与硫嘌呤诱导的白细胞减少症相关。然而，所测试的多态性仅占硫嘌呤诱发白细胞减少症风险的24.2%。