背景:硫唑嘌呤(AZA)是一种广泛使用的免疫抑制药物。白细胞减少是药物的严重不良反应,通常需要减少剂量或停药。白细胞减少症的预测因素包括遗传和非遗传因素。AZA代谢酶的遗传多态性,硫嘌呤S-甲基转移酶(TPMT)已建立。关于Nudix水解酶(NUDT15)基因多态性的作用尚无定论。这项病例对照研究评估了NUDT15和TPMT的遗传多态性与AZA诱导的白细胞减少症的关联。
方法:病例为在开始治疗1年内出现白细胞减少症(白细胞计数<4000/μl)的AZA患者,需要减少剂量或停药。在用AZA治疗的1年内没有白细胞减少的年龄和性别匹配的患者作为对照。TPMT(3个位点:c238G至C,c460G到A,c719A到G)和NUDT15(c415C到T,rs116855232)基因分型使用TPMT试纸条测定和聚合酶链反应-限制性片段长度多态性进行,分别。注意到基因型频率,计算比值比以确定基因型与白细胞减少症之间的关联。
结果:纳入29名受试者(15例和14例对照)。病例和对照之间的TPMT基因型(*1/*1和*1/*3C)未观察到统计学上的显着差异(P=0.23)。NUDT15基因型(*1/*1和*1/*3)(P=0.65)在病例和对照组之间也没有统计学上的显着差异。
结论:在印度东部人群中,上述基因型似乎与AZA诱导的白细胞减少症无关。
BACKGROUND: Azathioprine (AZA) is a widely used immunosuppressant drug. Leukopenia is a serious adverse effect of the drug which often necessitates dose reduction or drug withdrawal. Predictors of leukopenia include genetic and nongenetic factors. Genetic polymorphism of AZA-metabolizing enzyme, thiopurine S-methyltransferase (TPMT) is well established. There is inconclusive evidence about the role of Nudix hydrolase (NUDT15) gene polymorphism. This
case-control study assessed the association of genetic polymorphisms of NUDT15 and TPMT with leukopenia induced by AZA.
METHODS: Cases were patients on AZA who developed leukopenia (white blood cell count <4000/μl) within 1 year of treatment initiation that necessitated dose reduction or drug withdrawal. Age and gender-matched patients without leukopenia within 1 year of treatment with AZA served as controls. TPMT (3 loci: c238G to C, c460G to A, c719A to G) and NUDT15 (c 415C to T, rs116855232) genotyping were done using TPMT strip assay and polymerase chain reaction-restriction fragment length polymorphism, respectively. Genotype frequencies were noted, and the odds ratio was calculated to determine the association between genotypes and leukopenia.
RESULTS: Twenty-nine subjects (15 cases and 14 controls) were enrolled. Statistically significant differences were not observed in the TPMT genotype (*1/*1 and *1/*3C) (P = 0.23) between cases and controls. NUDT15 genotypes (*1/*1 and *1/*3) (P = 0.65) also showed no statistically significant difference between cases and controls.
CONCLUSIONS: The above genotypes do not appear to be associated with AZA-induced leukopenia in an eastern Indian population.