[1]张雪彤,潘萌.硫唑嘌呤的药物基因型及其在天疱疮治疗中的作用[J].中国皮肤性病学杂志,2020,(05):596-600.[doi:10.13735/j.cjdv.1001-7089.201905004]
 ZHANG Xuetong,PAN Meng.Genotypes of Azathioprine and its Role in the Treatment of Pemphigus[J].The Chinese Journal of Dermatovenereology,2020,(05):596-600.[doi:10.13735/j.cjdv.1001-7089.201905004]
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硫唑嘌呤的药物基因型及其在天疱疮治疗中的作用
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《中国皮肤性病学杂志》[ISSN:1001-7089/CN:61-1197/R]

卷:
期数:
2020年05期
页码:
596-600
栏目:
继续医学教育
出版日期:
2020-05-01

文章信息/Info

Title:
Genotypes of Azathioprine and its Role in the Treatment of Pemphigus
文章编号:
1001-7089(2020)05-0596-05
作者:
张雪彤潘萌
上海交通大学医学院附属瑞金医院皮肤科,上海 200025
Author(s):
ZHANG XuetongPAN Meng
(Department of Dermatology,Ruijin Hospital Affiliated to Medical College of Shanghai Jiaotong University,Shanghai 200025,China)
关键词:
硫唑嘌呤 天疱疮 NUDT
Keywords:
Azathioprine Pemphigus NUDT
分类号:
R 758.66
DOI:
10.13735/j.cjdv.1001-7089.201905004
文献标志码:
A
摘要:
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。
Abstract:
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.415C>T mutation in NUDT15,a negative regulator of activation of thiopurines,is closely related to leukopenia in the Asian population.Detection of NUDT c.415C>T is helpful to guide the individualized application of purines in pemphigus patients and reduce the long-term dosage of glucocorticoids in combination therapy.

参考文献/References:

[1] 沈如飞,曾繁典,师少军.硫唑嘌呤的药理作用和临床应用研究进展[J].中国药师,2013,16(9):1409-1412.
[2] Meyer V,Beissert S.Azathioprine in the treatment of autoimmune blistering diseases[J].Dermatol Clin,2011,29(4):545-554.
[3] Wang L,Weinshilboum R.Thiopurine S-methyltransferase pharmacogenetics:insights,challenges and future directions[J].Oncogene,2006,25(11):1629-1638.
[4] Karran P.Thiopurines,DNA damage,DNA repair and therapy-related cancer[J].Br Med Bull,2006,(79-80):153-170.
[5] Relling MV,GardnerEE,Sandborn WJ,et al.Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing:2013 update.[J].Clinical Pharmacol Ther,2013,93(4):324-325.
[6] 刘跃平,徐含青,杨翔,等.TPMT基因型在中国人群中的分布[J].临床检验杂志,2015,33(9):711-714.
[7] Schmiegelow K,Nielsen SN,Frandsen TL,et al.Mercaptopurine/ Methotrexate maintenance therapy of childhood acute lymphoblastic leukemia:clinical facts and fiction [J].J Pediatr Hematol Oncol,2014,36(7):503-517.
[8] 陈潇潇,沈树红.巯嘌呤的药物基因组学研究进展[J].中国当代儿科杂志,2017,19(9):1027-1033.
[9] Liang DC,Yang CP,Liu HC,et al.NUDT15 gene polymorphism related to mercaptopurine intolerance in Taiwan Chinese children with acute lymphoblastic leukemia[J].Pharmacogenomics J,2016,16(6):536-539.
[10] Chiengthong K,Ittiwut C,Muensri S,et al.NUDT15 c.415C>T increases risk of 6-mercaptopurine induced myelosuppression during maintenance therapy in children with acute lymphoblastic leukemia[J].Haematologica,2016,101(1):e24-e26.
[11] Yang SK,Hong M,Baek J,et al.A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia[J].Nat Genet,2014,46(9):1017-1020.
[12] Valerie NC,Hagenkort A,Page BD,et al.NUDT15 hydrolyzes 6-thio-deoxyGTP to mediate the anticancer efficacy of 6-thioguanine[J].Cancer Res,2016,76(18):5501-5511.
[13] Singh M,Bhatia P,Khera S,et al.Emerging role of NUDT15 polymorphisms in 6-mercaptopurine metabolism and dose related toxicity in acute lymphoblastic leukaemia[J].Leuk Res,2017,62:17-22.
[14] Moriyama T,Nishii R,Perez-Andreu V,et al.NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity[J].Nat Genet,2016,48(4):367-373.
[15] Neurath MF,Kiesslich R,Fischer C,et al.6-thioguanosine diphosphate and triphosphate levels in red blood cells and response to azathioprine therapy in Crohn's disease[J].Clin Gastroenterol Hepatol,2005,3(10):1007-1014.
[16] Nishii R,Moriyama T,Janke LJ,et al.Preclinical evaluation of NUDT15-guided thiopurine therapy and its effects on toxicity and anti-leukemic efficacy[J].Blood,2018,131(22):2466-2474.
[17] Wong FC,Leung AW,Kwok JS,et al.NUDT15 variant and thiopurine-induced leukopenia in Hong Kong[J].Hong Kong Med J,2016,22(2):185-187.
[18] Yan W,Zhou YH,Wang L,et al.NUDT15 polymorphism and severe azathioprine-induced myelosuppression in a Chinese man with pemphigus vulgaris[J].Br J Dermatol,2018,178(1):e40-e41.
[19] Shih YC,Zou YR,Wang B,et al.Azathioprine-induced myelosuppression intwo pemphigus vulgaris patients with homozygous polymorphism of NUDT15[J].J Dermatol,2019,46(2):e59-e61.
[20] Hertl M,Jedlickova H,Karpati S,et al.Pemphigus.S2 Guideline for diagnosis and treatment-guided By the European Dermatology Forum(EDF)in cooperation with the European Academy of Dermatology and Venereology(EADV)[J].J Eur Acad Dermatol Venereol,2015,29(3):405-414.
[21] Committee for guidelines for the management of pemphigus disease,Amagai M,Tanikawa A,et al.Japanese guidelines for the management of pemphigus[J].J Dermatol, 2014,41(6):471-486.
[22] 张弦,许人超,元慧杰,等.寻常型天疱疮63例疗效分析[J].江苏医药,2016,42(1):97-99.
[23] Chams-Davatchi C,Esmaili N,Daneshpazhooh M,et al.Randomized controlled open-label trial of four treatment regimens for pemphigus vulgaris[J].J Am Acad Dermatol,2007,57(4):622-628.
[24] Martin LK,Werth V,Villanueva E,et al.Interventions for pemphigus vulgaris and pemphigus foliaceus[J].Cochrane Database Syst Rev,2009,(1):CD006263.
[25] Lee YJ,Hwang EH,Park JH,et al.NUDT15 variant is the most common variant associated with thiopurine-induced early leukopenia and alopecia in Korean pediatric patients with Crohn's disease[J].Eur J Gastroenterol Hepatol,2016,28(4):475-478.

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备注/Memo

备注/Memo:
[基金项目] 国家自然科学基金重点项目(8173000414); 国家自然科学基金面上项目(81673064); 上海市科学技术委员会优秀学科带头人计划(17XD1402700)
[通信作者] 潘萌,E-mail:panmeng@medmail.com.cn
[Corresponding author] PAN Meng,E-mail:panmeng@medmail.com.cn
更新日期/Last Update: 2020-05-11