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. Xenobiotica. 2020 Aug 19;:1-7 Authors: Uno Y, Mikami T, Tsukazaki Y, Nakanishi Y, Murayama N, Ikushiro S, Tsusaki H, Yamazaki H Abstract 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 cynomolgus UGT1A1/6/9 have not been investigated. 2. We re-sequenced UGT1A1, UGT1A6, and UGT1A9 in 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 these UGT1A1, UGT1A6, and UGT1A9 variants, 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 the UGT1A1 mutation G69R was 23%, 28%, and 63% in cynomolgus macaques bred in Cambodia, China, and Indonesia, respectively, and 97% in rhesus macaques. 4. The O-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 for UGT1A1 G69R (n = 11) showed significantly reduced estradiol 3-O-glucuronidation activities compared with those from wild-type animal...
Source: Xenobiotica - Category: Research Authors: Tags: Xenobiotica Source Type: research