日本自身免疫性肝病患者的硫嘌呤S-甲基转移酶基因多态性

Thiopurine S-methyltransferase gene polymorphism in Japanese patients with autoimmune liver diseases.

作者信息

Tamori Akihiro, Shinzaki Mayumi, Kosaka Saori, Hayashi Takehiro, Iwai Shuji, Enomoto Masaru, Habu Daiki, Sakaguchi Hiroki, Kawada Norifumi, Hino Masayuki, Shiomi Susumu, Nishiguchi Shuhei

机构信息

Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.

出版信息

Liver Int. 2007 Feb;27(1):95-100. doi: 10.1111/j.1478-3231.2006.01392.x.

DOI:10.1111/j.1478-3231.2006.01392.x

PMID:17241387

Abstract

BACKGROUND AND AIM

Thiopurine S-methyltransferase (TPMT) genotypes or phenotypes may be a predictive factor for azathioprine-induced toxicities. We investigated the genotypic status of TPMT to evaluate the risk of azathioprine-related adverse effects in Japanese patients with different liver diseases, including autoimmune hepatitis (AIH).

METHODS

49 patients with AIH, 67 with primary biliary cirrhosis (PBC), and 120 with hepatitis C virus (HCV) were examined. TPMT genotypes were determined by PCR-restriction fragment length polymorphism-based assays.

RESULTS

The distribution of TPMT genotypes was 90% TPMT1/TPMT1, 8% TPMT1/TPMT3C, and 2% TPMT3C/TPMT3C in AIH, and 94% TPMT1/TPMT1, 4.5% TPMT1/TPMT3C, and 1.5% TPMT3C/TPMT3C in PBC. All except 1 patient with HCV had the TPMT1/TPMT1 genotype. Severe myelosuppression occurred in two of nine patients with AIH who received azathioprine, one of whom was homozygous for TPMT*3C.

CONCLUSIONS

TPMT*3C variants are more frequent in patients with AIH or PBC than in patients with viral hepatitis or healthy volunteers in Japan. Pharmacogenetic screening for TPMT polymorphisms before commencing azathioprine therapy may help to prevent severe hematotoxicity in patients with TPMT deficiency.

摘要

背景与目的

硫嘌呤甲基转移酶（TPMT）基因型或表型可能是硫唑嘌呤诱导毒性的预测因素。我们研究了TPMT的基因状态，以评估不同肝病的日本患者，包括自身免疫性肝炎（AIH）中与硫唑嘌呤相关不良反应的风险。

方法

对49例AIH患者、67例原发性胆汁性肝硬化（PBC）患者和120例丙型肝炎病毒（HCV）患者进行了检查。通过基于PCR-限制性片段长度多态性的检测方法确定TPMT基因型。

结果

AIH患者中TPMT基因型的分布为90%为TPMT1/TPMT1、8%为TPMT1/TPMT3C、2%为TPMT3C/TPMT3C；PBC患者中分别为94%、4.5%和1.5%。除1例HCV患者外，所有患者均为TPMT1/TPMT1基因型。接受硫唑嘌呤治疗的9例AIH患者中有2例发生了严重骨髓抑制，其中1例为TPMT*3C纯合子。