Genetic variants of UDP-glucuronosyltransferases 1A1, 1A6, and 1A9 in cynomolgus and rhesus macaques
Genetic variants of UDP-glucuronosyltransferases 1A1, 1A6, and 1A9 in cynomolgus and rhesus macaques
复制标题
食蟹猴和恒河猴中 UDP-葡萄糖醛酸基转移酶 1A1、1A6 和 1A9 的遗传变异
DOI：
10.1080/00498254.2020.1810367
复制
发表时间：
2020
期刊：
影响因子：
1.8
通讯作者：
Yamazaki Hiroshi
中科院分区：
文献类型：
--
作者：
Uno Yasuhiro;Mikami Takahiro;Tsukazaki Yasuko;Nakanishi Yasuharu;Murayama Norie;Ikushiro Shinichi;Tsusaki Hideshi;Yamazaki Hiroshi
1.在食蟹猴中，UDP-葡萄糖醛酸基转移酶（UGT）1A与其人类直系同源物具有相似的分子和酶特征。然而，在主要食蟹猴UGT 1A 1/6/9基因多态性尚未调查.我们对186只食蟹猴（在柬埔寨、中国或印度尼西亚饲养）和54只恒河猴的UGT 1A 1、UGT 1A 6和UGT 1A 9进行了重新测序，分别发现了15、13和26个非同义变体.在这些UGT 1A 1、UGT 1A 6和UGT 1A 9变体中，分别有10、9和12种为食蟹猴所特有; 4、1和2种为恒河猴所特有; 1、2和5种在食蟹猴和恒河猴中均发现。在柬埔寨、中国和印度尼西亚饲养的食蟹猴中，UGT 1A 1突变G69 R的频率分别为23%、28%和63%，在恒河猴中为97%.测定了食蟹猴和恒河猴肝微粒体对雌二醇、5-羟色胺和丙泊酚的O-葡萄糖醛酸化活性。在这些活性中，与野生型动物（n= 38）相比，UGT 1A 1G 69 R杂合子食蟹猴（n= 11）的肝微粒体显示雌二醇3-O-葡萄糖醛酸化活性显著降低。5.这些结果表明，遗传变异体（如UGT 1A 1G 69 R）可能影响食蟹猴和恒河猴中UGT 1A 1介导的药物葡萄糖醛酸化。
1. In the cynomolgus macaque, UDP-glucuronosyltransferases (UGTs) 1As have similar molecular and enzymatic characteristics to those of their human orthologs. However, genetic polymorphisms in major cynomolgusUGT1A1/6/9have not been investigated.2. We re-sequencedUGT1A1,UGT1A6, andUGT1A9in 186 cynomolgus macaques (bred in Cambodia, China, or Indonesia) and 54 rhesus macaques and found 15, 13, and 26 non-synonymous variants, respectively.3. Of theseUGT1A1,UGT1A6, andUGT1A9variants, respectively, 10, 9, and 12 were unique to cynomolgus macaques; 4, 1, and 2 were unique to rhesus macaques; and 1, 2, and 5 were found in both cynomolgus and rhesus macaques. The frequency of theUGT1A1mutation G69R was 23%, 28%, and 63% in cynomolgus macaques bred in Cambodia, China, and Indonesia, respectively, and 97% in rhesus macaques.4. TheO-glucuronidation activities of liver microsomes from cynomolgus and rhesus macaques with respect to estradiol, serotonin, and propofol were measured. Among these activities, liver microsomes from cynomolgus macaques heterozygous forUGT1A1G69R (n= 11) showed significantly reduced estradiol 3-O-glucuronidation activities compared with those from wild-type animals (n= 38).5. These results suggest genetic variants such asUGT1A1G69R could influence the UGT1A1-mediated glucuronidation of drugs in cynomolgus and rhesus macaques.
食蟹猴中谷胱甘肽 S-转移酶 GSTT1 和 GSTT2 的遗传变异：GSTT 底物和功能相关等位基因的鉴定。
影响因子：
4.1
作者：
Y. Uno;N. Murayama;Masami Kato;Saki Tanaka;Tomoko Ohkoshi;H. Yamazaki
通讯作者：
H. Yamazaki
影响因子：
2.6
作者：
Minami, Hironobu;Sai, Kimie;Saijo, Nagahiro
通讯作者：
Saijo, Nagahiro
普通狨猴中功能性 UDP-葡萄糖醛酸基转移酶 1A、2B 的分子特征。
影响因子：
5.8
作者：
Y. Uno;Shotaro Uehara;Takashi Inoue;Shu Kawamura;N. Murayama;Miyu Nishikawa;S. Ikushiro;E. Sasaki;H. Yamazaki
通讯作者：
H. Yamazaki