Carboxylesterase 1A2 encoding gene with increased transcription and potential rapid drug metabolism in Asian populations
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Carboxylesterase 1A2 encoding gene with increased transcription and potential rapid drug metabolism in Asian populations. / Rasmussen, Henrik Berg; Madsen, Majbritt Busk; Lyauk, Yassine Kamal; Hansen, Peter Riis; Hughes, Timothy.
In: Drug Metabolism and Drug Interactions, Vol. 32, No. 3, 09.2017, p. 163-168.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Carboxylesterase 1A2 encoding gene with increased transcription and potential rapid drug metabolism in Asian populations
AU - Rasmussen, Henrik Berg
AU - Madsen, Majbritt Busk
AU - Lyauk, Yassine Kamal
AU - Hansen, Peter Riis
AU - Hughes, Timothy
PY - 2017/9
Y1 - 2017/9
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1515/dmpt-2017-0012
DO - 10.1515/dmpt-2017-0012
M3 - Journal article
C2 - 28803225
VL - 32
SP - 163
EP - 168
JO - Drug Metabolism and Drug Interactions
JF - Drug Metabolism and Drug Interactions
SN - 2363-8907
IS - 3
ER -
ID: 185623909