Rasmussen Henrik Berg, Madsen Majbritt Busk, Lyauk Yassine Kamal, Hansen Peter Riis, Hughes Timothy
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Drug Metab Pers Ther. 2017 Sep 26;32(3):163-168. doi: 10.1515/dmpt-2017-0012.
The carboxylesterase 1 gene (CES1) encodes a hydrolase implicated in the metabolism of commonly used drugs. CES1A2, a hybrid of CES1 and a CES1-like pseudogene, has a promoter that is weak in most individuals. However, some individuals harbor a promoter haplotype of this gene with two overlapping Sp1 sites that confer significantly increased transcription potentially leading to rapid drug metabolism. This CES1A2 haplotype has previously been reported to be common among Asians. Using polymerase chain reaction followed by sequencing, the present study examined variation in the promoter and 5' untranslated region of CES1A2 in 120 Han Chinese and 120 Japanese people enrolled in the 1000 Genomes Project. We identified 11 single nucleotide variations, two of which were novel, in 145 of the individuals who were found to carry CES1A2. Alignment analysis indicated that the CES1A2 haplotype with the overlapping Sp1 sites has been generated by incorporation of a segment of CES1. All minor allele frequencies were equal to or below 0.022 and the frequencies of the minor haplotypes were up to 40-fold lower than previously reported, including that of the haplotype with the overlapping Sp1 sites. This information is novel and suggests that the pharmacogenetic relevance of CES1A2 is limited in Asians.
羧酸酯酶1基因（CES1）编码一种参与常用药物代谢的水解酶。CES1A2是CES1与一个类似CES1的假基因的杂交体，其启动子在大多数个体中活性较弱。然而，一些个体携带该基因的一种启动子单倍型，具有两个重叠的Sp1位点，可显著增加转录，可能导致药物快速代谢。此前有报道称这种CES1A2单倍型在亚洲人中很常见。本研究采用聚合酶链反应后测序的方法，检测了参与千人基因组计划的120名汉族人和120名日本人中CES1A2启动子和5'非翻译区的变异情况。我们在145名携带CES1A2的个体中鉴定出11个单核苷酸变异，其中两个是新发现的。比对分析表明，具有重叠Sp1位点的CES1A2单倍型是通过掺入一段CES1产生的。所有次要等位基因频率均等于或低于0.022，次要单倍型的频率比之前报道的低40倍，包括具有重叠Sp1位点的单倍型。这些信息是新的，表明CES1A2在亚洲人中的药物遗传学相关性有限。
