硫唑嘌呤的药物基因型及其在天疱疮治疗中的作用

Genotypes of Azathioprine and its Role in the Treatment of Pemphigus

硫唑嘌呤是最常用于天疱疮的免疫抑制剂之一,但骨髓抑制和肝肾毒性等不良反应限制了其临床应用。TPMT基因突变引起的活性下降与硫唑嘌呤的不耐受有关,但亚洲人群该位点突变频率较低。近期研究发现,NUDT15 c.415 C>T基因突变与亚洲人群的白细胞减少症等副作用的关系更为密切,该位点的检测有利于指导嘌呤类药物在天疱疮患者中的个体化应用,减少联合治疗方案中糖皮质激素的长期用量。

Azathioprine(AZA) is one of the most commonly used immunosuppressant in pemphigus vulgaris,but adverse reactions such as bone marrow suppression and hepatorenal toxicity limit its clinical application.The decreased activity of TPMT gene,the main enzyme involved in the metabolism of thiopurines,such as AZA,caused by mutations,is related to AZA intolerance.However,the frequency of the mutations in TPMT gene is low in the Asian population.Recent studies have found that c.415 C>T mutation in NUDT15,a negative regulator of activation of thiopurines,is closely related to leukopenia in the Asian population.Detection of NUDT c.415 C>T is helpful to guide the individualized application of purines in pemphigus patients and reduce the long-term dosage of glucocorticoids in combination therapy.