Rotor syndrome is caused by digenic loss-of-function variants in SLCO1B1 and SLCO1B3 but only a few studies have reported co-occurring inactivating variants from both genes. A rotor syndrome-causing long interspersed element-1 (LINE-1) insertion in SLCO1B3 had been reported to be highly prevalent in the Japanese population but there has been no additional report. In spite of its known association with various human diseases, LINE-1 is hard to detect with current sequencing technologies. In this study, we aimed to devise a method to screen the LINE-1 insertion variant and investigate the frequency of this variant in various populations. A chimeric sequence, that was generated by concatenating the reference sequence at the junction and a part of inserted LINE-1 sequence, was searched from 725 raw sequencing data files. In cases containing the chimeric sequence, confirmatory long-range PCR and gap-PCR were performed. In total, 95 (13.1%) of 725 patients were positive for the chimeric sequence, and all were confirmed to have the SLCO1B3 LINE-1 insertion by PCR-based tests. The same chimeric sequence was searched from the 1000 Genomes Project data repository and the carrier frequency was remarkably high in the East Asian populations (10.1%), especially in Southern Han Chinese (18.5%), but almost absent in other populations. This SLCO1B3 LINE-1 insertion should be screened in a population-specific manner under suspicion of Rotor syndrome and the methods proposed in this study would enable this in a simple way.

转子综合征是由SLCO1B1和SLCO1B3中的双基因功能丧失变异引起的，但只有少数研究报告了这两个基因同时发生的失活变异。转子综合征导致SLCO1B3中的长散布元素 1 (LINE-1) 插入据报道，它在日本人口中非常流行，但没有其他报告。尽管已知 LINE-1 与各种人类疾病有关，但目前的测序技术很难检测到 LINE-1。在这项研究中，我们旨在设计一种方法来筛选 LINE-1 插入变体并调查该变体在不同人群中的频率。从 725 个原始测序数据文件中搜索了一个嵌合序列，该序列是通过连接连接处的参考序列和插入的 LINE-1 序列的一部分而生成的。在包含嵌合序列的情况下，进行了确认性长程 PCR 和间隙 PCR。总共有 725 名患者中有 95 名（13.1%）的嵌合序列呈阳性，并且所有患者都被证实患有SLCO1B3通过基于 PCR 的测试插入 LINE-1。从 1000 Genomes Project 数据库中搜索到相同的嵌合序列，东亚人群中的携带频率非常高（10.1%），特别是在南方汉族（18.5%）中，但在其他人群中几乎没有。这种SLCO1B3 LINE-1 插入应在怀疑转子综合征的情况下以特定人群的方式进行筛选，本研究中提出的方法将以简单的方式实现这一点。