Thiopurine S-methyltransferase pharmacogenetics in a large-scale healthy Italian-Caucasian population: differences in enzyme activity.
Thiopurine S-methyltransferase pharmacogenetics in a large-scale healthy Italian-Caucasian population: differences in enzyme activity.
复制标题
大规模健康意大利高加索人群中的硫嘌呤 S-甲基转移酶药物遗传学：酶活性的差异。
DOI：
10.2217/pgs.09.103
复制
发表时间：
2009
期刊：
影响因子：
2.1
通讯作者：
R. Canaparo
中科院分区：
文献类型：
--
作者：
L. Serpe;P. Calvo;E. Muntoni;S. D’antico;M. Giaccone;A. Avagnina;M. Baldi;C. Barbera;F. Curti;A. Pera;M. Eandi;G. Zara;R. Canaparo
目标
目的：探讨基因、年龄和性别对健康意大利高加索人群硫嘌呤S甲基转移酶表型的影响。
材料与方法
本研究调查了943名不同年龄和性别(年龄范围：0.08-68岁；623名男性，320名女性)健康意大利裔高加索人的TPMT基因和TPMT表型。测定所有样本的TPMT红细胞活性，并确定TPMT等位基因*2、*3A、*3B和*3C的基因型。
结果
我们所有人口的TPMT活性水平从1.6到75.2U/GHb不等。野生型和杂合型受试者之间的TPMT活性有显著差异。我们根据频率分布将TPMT活性分为四类：低(0.1%)、中(32.9%)、正常(60%)和高(7%)，任意截止值分别为8.0、19.4和37.0U/GHb。野生型纯合子占94.5%，杂合型占5.4%，TPMT*3B/*3C复合杂合型占0.1%。TPMT基因分型与表型的总符合率为71.6%。野生型儿童(0.08~17岁)的TPMT活性显著高于野生型成人(18~68岁)。此外，0.08-5岁野生型婴儿的TPMT活性比其他野生型婴儿平均高9%，并且只有0.08-2岁儿童的TPMT活性男性高于女性。
结论
本研究获得的数据表明，遗传因素似乎是成人TPMT表型变异的主要方面，而在儿童中，在评估TPMT表型时应考虑其他生理因素，如年龄和性别。
AIMS
To investigate the influence of genotype, age and gender on the thiopurine S-methyltransferase (TPMT) phenotype in healthy Italian-Caucasian subjects.
MATERIALS & METHODS
The study investigated the TPMT genotype and the TPMT phenotype of 943 healthy Italian-Caucasian subjects of different age and gender (age range: 0.08-68 years; 623 males 320 females). TPMT red blood cell activity was measured in all samples and genotype was determined for the TPMT alleles *2, *3A, *3B and *3C.
RESULTS
TPMT activity levels in our whole population ranged from 1.6 up to 75.2 U/gHb. Significant TPMT activity differences between wild-type and heterozygous subjects were observed. We divided our TPMT activity into four categories according to our frequency distribution: low (0.1%), intermediate (32.9%), normal (60%) and high (7%), with arbitrary cut-off values of 8.0, 19.4 and 37.0 U/gHb, respectively. The whole population had a total of 94.5% of homozygous wild-type subjects, 5.4% heterozygous variants and one (0.1%) compound heterozygous variant TPMT*3B/*3C. The overall concordance rate between TPMT genotypes and phenotypes was 71.6%. The TPMT activity was significantly higher in wild-type children (0.08-17 years) than in wild-type adults (aged 18-68 years). Moreover, it was noted that wild-type infants from 0.08 to 5 years had a 9% higher average TPMT activity than the other wild-type groups, and only in children from 0.08 to 2 years was the TPMT activity higher in males than in females.
CONCLUSION
The data obtained in this study show that genetic factors seem to be the major aspect in TPMT phenotype variability in adults, whilst, in children, other physiological factors should be taken into consideration when assessing the TPMT phenotype, such as age and gender.
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影响因子：
5.8
作者：
WOODSON, LC;WEINSHILBOUM, RM
通讯作者：
WEINSHILBOUM, RM
影响因子：
3.1
作者：
Pan, Tung-Ming;Wu, Tin-Wei
通讯作者：
Wu, Tin-Wei
人肝硫嘌呤甲基转移酶药物遗传学：生化特性、肝-红细胞相关性和同工酶的存在。
DOI：
--
发表时间：
1992
期刊：
Pharmacogenetics
影响因子：
--
作者：
Szumlanski,CL;Honchel,R;Scott,MC;Weinshilboum,RM
通讯作者：
Weinshilboum,RM
大鼠硫嘌呤甲基转移酶：睾酮的调节。
DOI：
--
发表时间：
1981
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Woodson,LC;Maus,TP;Reiter,C;Weinshilboum,RM
通讯作者：
Weinshilboum,RM