Carboxylesterase 1A2 encoding gene with increased transcription and potential rapid drug metabolism in Asian populations

Henrik Berg Rasmussen, Majbritt Busk Madsen, Yassine Kamal Lyauk, Peter Riis Hansen, Timothy Hughes

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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
OriginalsprogEngelsk
TidsskriftDrug Metabolism and Personalized Therapy
Vol/bind32
Udgave nummer3
Sider (fra-til)163–168
ISSN2363-8907
DOI
StatusUdgivet - 2017

Emneord

  • asian ppulations
  • carboxylesterase
  • 1a2 gene
  • polymorhisms
  • promoter
  • transcriptional activity

Citer dette

Rasmussen, Henrik Berg ; Madsen, Majbritt Busk ; Lyauk, Yassine Kamal ; Hansen, Peter Riis ; Hughes, Timothy. / Carboxylesterase 1A2 encoding gene with increased transcription and potential rapid drug metabolism in Asian populations. I: Drug Metabolism and Personalized Therapy. 2017 ; Bind 32, Nr. 3. s. 163–168.
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title = "Carboxylesterase 1A2 encoding gene with increased transcription and potential rapid drug metabolism in Asian populations",
abstract = "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",
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author = "Rasmussen, {Henrik Berg} and Madsen, {Majbritt Busk} and Lyauk, {Yassine Kamal} and Hansen, {Peter Riis} and Timothy Hughes",
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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.

I: Drug Metabolism and Personalized Therapy, Bind 32, Nr. 3, 2017, s. 163–168.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

Y1 - 2017

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 - asian ppulations

KW - carboxylesterase

KW - 1a2 gene

KW - polymorhisms

KW - promoter

KW - transcriptional activity

KW - aisan populations

KW - carboxylesterase

KW - 1a2 gene

KW - polymorphisms

KW - promoter

KW - transcriptional activity

U2 - 10.1515/dmpt-2017-0012

DO - 10.1515/dmpt-2017-0012

M3 - Journal article

VL - 32

SP - 163

EP - 168

JO - Drug Metabolism and Personalized Therapy

JF - Drug Metabolism and Personalized Therapy

SN - 2363-8907

IS - 3

ER -