TPMT启动子区域串联重复序列可变数目的新型基序以及串联重复序列可变数目与TPMT*3等位基因的进化关联。
Novel motif of variable number of tandem repeats in TPMT promoter region and evolutionary association of variable number of tandem repeats with TPMT*3 alleles.
作者信息
Urbančič Dunja, Šmid Alenka, Stocco Gabriele, Decorti Giuliana, Mlinarič-Raščan Irena, Karas Kuželički Nataša
机构信息
Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia.
Department of Life Sciences, University of Trieste, 34127 Trieste, Italy.
出版信息
Pharmacogenomics. 2018 Nov;19(17):1311-1322. doi: 10.2217/pgs-2018-0123. Epub 2018 Oct 22.
AIM
SNPs in the gene for TPMT exemplify one of the most successful translations of pharmacogenomics into clinical practice. This study explains the correlation between common SNPs and variable number of tandem repeats (VNTR) in promoter of the gene.
MATERIALS & METHODS: We determined VNTR polymorphisms, as well as TPMT2 and TPMT3 SNPs and TPMT activity in Slovenian and Italian individuals and lymphoblastoid cell lines.
RESULTS
We observed a previously unreported VNTR allele, AB7C, in a TPMT3A heterozygous individual. VNTRs with two (AB2C) and three or more (ABnC, n ≥ 3) B motifs were statistically significant in complete linkage disequilibrium (D' = 1, r = 1, p < 0.0001) with the TPMT3C and TPMT*3A alleles, respectively.
CONCLUSION
The study provides insights into the stepwise evolution of TPMT*3 alleles from *3C to *3A, with increasing number of B motifs in the VNTR region.
目的
硫嘌呤甲基转移酶（TPMT）基因中的单核苷酸多态性（SNPs）是药物基因组学在临床实践中最成功的转化实例之一。本研究解释了该基因启动子区常见SNPs与可变串联重复序列（VNTR）数量之间的相关性。
材料与方法
我们测定了斯洛文尼亚人和意大利人以及淋巴母细胞系中的VNTR多态性、TPMT2和TPMT3 SNPs以及TPMT活性。
结果
我们在一名TPMT3A杂合个体中观察到一个先前未报道的VNTR等位基因AB7C。含有两个B基序（AB2C）和三个或更多B基序（ABnC，n≥3）的VNTR分别与TPMT3C和TPMT*3A等位基因处于完全连锁不平衡状态（D' = 1，r = 1，p < 0.0001），具有统计学意义。
结论
该研究揭示了TPMT3等位基因从3C到*3A的逐步进化过程，VNTR区域中的B基序数量不断增加。
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