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...
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ftdatacite:10.17877/de290r-19957 2023-05-15T16:28:27+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/10.17877/de290r-19957 https://eldorado.tu-dortmund.de/handle/2003/37972 en eng Technische Universität Dortmund Creative Commons Attribution 4.0 International https://creativecommons.org/licenses/by/4.0/legalcode cc-by-4.0 CC-BY N-acetyltransferase 2 Greenland NAT2 genotype status NAT2 enzyme activity Caffeine test Isoniazid 610 Text article (journal) article-journal ScholarlyArticle 2018 ftdatacite https://doi.org/10.17877/de290r-19957 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 pH<3, a deviation from the standard protocol due to the field work character of the study, where immediate pH adjustment to pH=3.5 was not possible. We excluded these samples. For the remaining 143 individuals with pH>3, 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;Vol. 17 2018 Text Greenland greenlandic inuit DataCite Metadata Store (German National Library of Science and Technology) Greenland |
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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 610 |
spellingShingle |
N-acetyltransferase 2 Greenland NAT2 genotype status NAT2 enzyme activity Caffeine test Isoniazid 610 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 610 |
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 pH<3, a deviation from the standard protocol due to the field work character of the study, where immediate pH adjustment to pH=3.5 was not possible. We excluded these samples. For the remaining 143 individuals with pH>3, 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;Vol. 17 2018 |
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 |
Technische Universität Dortmund |
publishDate |
2018 |
url |
https://dx.doi.org/10.17877/de290r-19957 https://eldorado.tu-dortmund.de/handle/2003/37972 |
geographic |
Greenland |
geographic_facet |
Greenland |
genre |
Greenland greenlandic inuit |
genre_facet |
Greenland greenlandic inuit |
op_rights |
Creative Commons Attribution 4.0 International https://creativecommons.org/licenses/by/4.0/legalcode cc-by-4.0 |
op_rightsnorm |
CC-BY |
op_doi |
https://doi.org/10.17877/de290r-19957 |
_version_ |
1766018111672156160 |