Study of correlation between the NAT2 phenotype and genotype status among Greenlandic Inuit
N-acetyltransferase 2 (NAT2) is the main enzyme metabolizing isoniazid and genotype-based treatment has been studied for years without becoming common practice. To investigate whether genotype-based isoniazid treatment is feasible in Greenland, we sequenced the coding sequence of NAT2 and determined...
Main Authors: | , , , , , , , , , , , , , , , |
---|---|
Format: | Text |
Language: | English |
Published: |
IfADo - Leibniz Research Centre for Working Environment and Human Factors, Dortmund
2018
|
Subjects: | |
Online Access: | https://dx.doi.org/10.17179/excli2018-1671 https://www.excli.de/vol17/Geller_02112018_proof.pdf |
id |
ftdatacite:10.17179/excli2018-1671 |
---|---|
record_format |
openpolar |
spelling |
ftdatacite:10.17179/excli2018-1671 2023-05-15T16:28:15+02:00 Study of correlation between the NAT2 phenotype and genotype status among Greenlandic Inuit Birch Kristensen, Emilie Yakimov, Victor Bjorn-Mortensen, Karen Soborg, Bolette Koch, Anders Andersson, Mikael Birch Kristensen, Kasper Michelsen, Sascha Wilk Skotte, Line Ahrendt Bjerregaard, Anne Blaszkewicz, Meinolf Golka, Klaus Hengstler, Jan G. Feenstra, Bjarke Melbye, Mads Geller, Frank 2018 https://dx.doi.org/10.17179/excli2018-1671 https://www.excli.de/vol17/Geller_02112018_proof.pdf en eng IfADo - Leibniz Research Centre for Working Environment and Human Factors, Dortmund http://www.excli.de/vol17/Geller_02112018_supplementary_information.xlsx This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/4.0/). CC-BY N-acetyltransferase 2 Greenland NAT2 genotype status NAT2 enzyme activity caffeine test isoniazid Text article-journal ScholarlyArticle 2018 ftdatacite https://doi.org/10.17179/excli2018-1671 2021-11-05T12:55:41Z N-acetyltransferase 2 (NAT2) is the main enzyme metabolizing isoniazid and genotype-based treatment has been studied for years without becoming common practice. To investigate whether genotype-based isoniazid treatment is feasible in Greenland, we sequenced the coding sequence of NAT2 and determined the NAT2 enzyme-activity by caffeine test. No additional genetic variants were identified in the coding sequence of NAT2, so that genotype status in 260 study participants could be assessed by a well-established 7-SNP panel. Studying the enzyme activity by the ratio of the two caffeine metabolites AFMU and 1X in 260 participants showed a high rate of slow phenotypes with intermediate or rapid genotype. These misclassifications were mainly observed in urine samples with pH3, we observed a moderate level of discrepancies (19 of the 116 individuals with intermediate or rapid genotype status having a slow phenotype). Further investigation showed that drinking coffee and not tea or cola was the most important factor for high levels of both metabolites. The concordance between phenotype and genotype status with regard to slow metabolism supported the recommendation of lower isoniazid doses in individuals with slow genotype status in order to avoid liver injury, a frequent side effect. The phenotypical variation observed for individuals with intermediate or rapid genotype status warrants further research before increased dosing of isoniazid can be recommended. : EXCLI Journal; 17:Doc1043; ISSN 1611-2156 Text Greenland greenlandic inuit DataCite Metadata Store (German National Library of Science and Technology) Greenland |
institution |
Open Polar |
collection |
DataCite Metadata Store (German National Library of Science and Technology) |
op_collection_id |
ftdatacite |
language |
English |
topic |
N-acetyltransferase 2 Greenland NAT2 genotype status NAT2 enzyme activity caffeine test isoniazid |
spellingShingle |
N-acetyltransferase 2 Greenland NAT2 genotype status NAT2 enzyme activity caffeine test isoniazid Birch Kristensen, Emilie Yakimov, Victor Bjorn-Mortensen, Karen Soborg, Bolette Koch, Anders Andersson, Mikael Birch Kristensen, Kasper Michelsen, Sascha Wilk Skotte, Line Ahrendt Bjerregaard, Anne Blaszkewicz, Meinolf Golka, Klaus Hengstler, Jan G. Feenstra, Bjarke Melbye, Mads Geller, Frank Study of correlation between the NAT2 phenotype and genotype status among Greenlandic Inuit |
topic_facet |
N-acetyltransferase 2 Greenland NAT2 genotype status NAT2 enzyme activity caffeine test isoniazid |
description |
N-acetyltransferase 2 (NAT2) is the main enzyme metabolizing isoniazid and genotype-based treatment has been studied for years without becoming common practice. To investigate whether genotype-based isoniazid treatment is feasible in Greenland, we sequenced the coding sequence of NAT2 and determined the NAT2 enzyme-activity by caffeine test. No additional genetic variants were identified in the coding sequence of NAT2, so that genotype status in 260 study participants could be assessed by a well-established 7-SNP panel. Studying the enzyme activity by the ratio of the two caffeine metabolites AFMU and 1X in 260 participants showed a high rate of slow phenotypes with intermediate or rapid genotype. These misclassifications were mainly observed in urine samples with pH3, we observed a moderate level of discrepancies (19 of the 116 individuals with intermediate or rapid genotype status having a slow phenotype). Further investigation showed that drinking coffee and not tea or cola was the most important factor for high levels of both metabolites. The concordance between phenotype and genotype status with regard to slow metabolism supported the recommendation of lower isoniazid doses in individuals with slow genotype status in order to avoid liver injury, a frequent side effect. The phenotypical variation observed for individuals with intermediate or rapid genotype status warrants further research before increased dosing of isoniazid can be recommended. : EXCLI Journal; 17:Doc1043; ISSN 1611-2156 |
format |
Text |
author |
Birch Kristensen, Emilie Yakimov, Victor Bjorn-Mortensen, Karen Soborg, Bolette Koch, Anders Andersson, Mikael Birch Kristensen, Kasper Michelsen, Sascha Wilk Skotte, Line Ahrendt Bjerregaard, Anne Blaszkewicz, Meinolf Golka, Klaus Hengstler, Jan G. Feenstra, Bjarke Melbye, Mads Geller, Frank |
author_facet |
Birch Kristensen, Emilie Yakimov, Victor Bjorn-Mortensen, Karen Soborg, Bolette Koch, Anders Andersson, Mikael Birch Kristensen, Kasper Michelsen, Sascha Wilk Skotte, Line Ahrendt Bjerregaard, Anne Blaszkewicz, Meinolf Golka, Klaus Hengstler, Jan G. Feenstra, Bjarke Melbye, Mads Geller, Frank |
author_sort |
Birch Kristensen, Emilie |
title |
Study of correlation between the NAT2 phenotype and genotype status among Greenlandic Inuit |
title_short |
Study of correlation between the NAT2 phenotype and genotype status among Greenlandic Inuit |
title_full |
Study of correlation between the NAT2 phenotype and genotype status among Greenlandic Inuit |
title_fullStr |
Study of correlation between the NAT2 phenotype and genotype status among Greenlandic Inuit |
title_full_unstemmed |
Study of correlation between the NAT2 phenotype and genotype status among Greenlandic Inuit |
title_sort |
study of correlation between the nat2 phenotype and genotype status among greenlandic inuit |
publisher |
IfADo - Leibniz Research Centre for Working Environment and Human Factors, Dortmund |
publishDate |
2018 |
url |
https://dx.doi.org/10.17179/excli2018-1671 https://www.excli.de/vol17/Geller_02112018_proof.pdf |
geographic |
Greenland |
geographic_facet |
Greenland |
genre |
Greenland greenlandic inuit |
genre_facet |
Greenland greenlandic inuit |
op_relation |
http://www.excli.de/vol17/Geller_02112018_supplementary_information.xlsx |
op_rights |
This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/4.0/). |
op_rightsnorm |
CC-BY |
op_doi |
https://doi.org/10.17179/excli2018-1671 |
_version_ |
1766017882932641792 |