Association of thiopurine methyltransferase status with azathioprine side effects in Chinese patients with systemic lupus erythematosus

被引：30

作者：

Chen, Dongying ^{[1
]}

Lian, Fan ^{[1
]}

Yuan, Shiwen ^{[1
]}

Wang, Yixi ^{[2
]}

Zhan, Zhongping ^{[1
]}

Ye, Yujin ^{[1
]}

Qiu, Qian ^{[1
]}

Xu, Hanshi ^{[1
]}

Liang, Liuqin ^{[1
]}

Yang, Xiuyan ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Rheumatol, Guangzhou 510080, Guangdong, Peoples R China

[2] Guangzhou Univ Med Sci, Affiliated Hosp 2, Dept Pharm, Guangzhou 510260, Guangdong, Peoples R China

来源：

CLINICAL RHEUMATOLOGY | 2014年 / 33卷 / 04期

基金：

中国国家自然科学基金;

关键词：

Adverse effects; Azathioprine; Genotype; Phenotype; Systemic lupus erythematosus; Thiopurine methyltransferase; INFLAMMATORY-BOWEL-DISEASE; S-METHYLTRANSFERASE; ETHNIC-GROUPS; GENOTYPE; THERAPY; MYELOSUPPRESSION; POLYMORPHISM; POPULATION; TRIAL;

D O I：

10.1007/s10067-013-2441-x

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Azathioprine (AZA) is indicated for the treatment of systemic lupus erythematosus (SLE). Thiopurine methyltransferase (TPMT) is the rate-limiting enzyme in the steps of AZA metabolization. Heritable deficiency of TPMT enzyme activity and polymorphisms may lead to leukopenia. This study aims to detect TPMT polymorphisms and TPMT enzyme activity in Chinese SLE patients and to describe the association between TPMT genotypes and adverse effects of AZA. One hundred and twenty-six SLE patients with present or previous thiopurine therapy were identified from a local database. Adverse effects were documented. No TPMT*2, TPMT*3A, or TPMT*3B mutant alleles were detected. TPMT*3C was detected in four patients (3.17 %). The heterozygotes had significantly lower mean TPMT activity as compared to the homozygotes (2.38 +/- 1.24 vs. 12.56 +/- 7.02 U/mL, P < 0.001). Twenty-seven cases (21.42 %) exhibited adverse effects. All of the heterozygotes (4/4, 100 %) developed severe leukopenia, and three cases (3/4, 75 %) of whom exhibited alopecia simultaneously. The specificity of TPMT*3C for predicting leukopenia and alopecia was 100 and 99.17 %, respectively, and the sensitivity was 28.57 and 60.00 %, respectively. The mean value of TPMT activity with leukopenia (4.67 +/- 3.01 vs. 13.2 +/- 6.94 U/mL RBC, P < 0.001) or alopecia (2.31 +/- 1.16 vs. 12.65 +/- 6.98 U/mL RBC, P < 0.001) was significantly lower than those without. TPMT*3C was the most common mutant polymorphism found in the study group. TPMT activity is reduced in TPMT*3C mutant. AZA-induced leukopenia and alopecia were partly correlated to TPMT*3C heterozygotes and low TPMT activity. The results of this study suggest that the value of TPMT genotyping before AZA therapy was limited in Chinese SLE patients, considering the low sensitivity. Routine monitoring of TPMT activity before prescribing and continuous hematological monitoring dose were recommended.

引用

页码：499 / 503

页数：5

共 24 条

[1]

Azathioprine-induced fatal myelosuppression in systemic lupus erythematosus patient carrying TPMT*3C polymorphism [J].