Study of correlation between the NAT2 phenotype and genotype status among greenlandic inuit

Research output: Contribution to journalJournal articlepeer-review

Standard

Study of correlation between the NAT2 phenotype and genotype status among greenlandic inuit. / Kristensen, Emilie Birch; Yakimov, Victor; Bjørn-Mortensen, Karen; Soborg, Bolette; Koch, Anders; Andersson, Mikael; Kristensen, Kasper Birch; Michelsen, Sascha Wilk; Skotte, Line; Bjerregaard, Anne Ahrendt; Blaszkewicz, Meinolf; Golka, Klaus; Hengstler, Jan G.; Feenstra, Bjarke; Melbye, Mads; Geller, Frank.

In: EXCLI Journal, Vol. 17, 2018, p. 1043-1053.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Kristensen, EB, Yakimov, V, Bjørn-Mortensen, K, Soborg, B, Koch, A, Andersson, M, Kristensen, KB, Michelsen, SW, Skotte, L, Bjerregaard, AA, Blaszkewicz, M, Golka, K, Hengstler, JG, Feenstra, B, Melbye, M & Geller, F 2018, 'Study of correlation between the NAT2 phenotype and genotype status among greenlandic inuit', EXCLI Journal, vol. 17, pp. 1043-1053. <https://www.excli.de/index.php/excli/article/view/660>

APA

Kristensen, E. B., Yakimov, V., Bjørn-Mortensen, K., Soborg, B., Koch, A., Andersson, M., Kristensen, K. B., Michelsen, S. W., Skotte, L., Bjerregaard, A. A., Blaszkewicz, M., Golka, K., Hengstler, J. G., Feenstra, B., Melbye, M., & Geller, F. (2018). Study of correlation between the NAT2 phenotype and genotype status among greenlandic inuit. EXCLI Journal, 17, 1043-1053. https://www.excli.de/index.php/excli/article/view/660

Vancouver

Kristensen EB, Yakimov V, Bjørn-Mortensen K, Soborg B, Koch A, Andersson M et al. Study of correlation between the NAT2 phenotype and genotype status among greenlandic inuit. EXCLI Journal. 2018;17:1043-1053.

Author

Kristensen, Emilie Birch ; Yakimov, Victor ; Bjørn-Mortensen, Karen ; Soborg, Bolette ; Koch, Anders ; Andersson, Mikael ; Kristensen, Kasper Birch ; Michelsen, Sascha Wilk ; Skotte, Line ; Bjerregaard, Anne Ahrendt ; 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. In: EXCLI Journal. 2018 ; Vol. 17. pp. 1043-1053.

Bibtex

@article{cefbde5911ca40f6a1011b69f3f6ca5c,
title = "Study of correlation between the NAT2 phenotype and genotype status among greenlandic inuit",
abstract = "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.",
keywords = "Caffeine test, Greenland, Isoniazid, N-acetyltransferase 2, NAT2 enzyme activity, NAT2 genotype status",
author = "Kristensen, {Emilie Birch} and Victor Yakimov and Karen Bj{\o}rn-Mortensen and Bolette Soborg and Anders Koch and Mikael Andersson and Kristensen, {Kasper Birch} and Michelsen, {Sascha Wilk} and Line Skotte and Bjerregaard, {Anne Ahrendt} and Meinolf Blaszkewicz and Klaus Golka and Hengstler, {Jan G.} and Bjarke Feenstra and Mads Melbye and Frank Geller",
year = "2018",
language = "English",
volume = "17",
pages = "1043--1053",
journal = "EXCLI Journal",
issn = "1611-2156",
publisher = "University of Mainz",

}

RIS

TY - JOUR

T1 - Study of correlation between the NAT2 phenotype and genotype status among greenlandic inuit

AU - Kristensen, Emilie Birch

AU - Yakimov, Victor

AU - Bjørn-Mortensen, Karen

AU - Soborg, Bolette

AU - Koch, Anders

AU - Andersson, Mikael

AU - Kristensen, Kasper Birch

AU - Michelsen, Sascha Wilk

AU - Skotte, Line

AU - Bjerregaard, Anne Ahrendt

AU - Blaszkewicz, Meinolf

AU - Golka, Klaus

AU - Hengstler, Jan G.

AU - Feenstra, Bjarke

AU - Melbye, Mads

AU - Geller, Frank

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Caffeine test

KW - Greenland

KW - Isoniazid

KW - N-acetyltransferase 2

KW - NAT2 enzyme activity

KW - NAT2 genotype status

M3 - Journal article

AN - SCOPUS:85056735601

VL - 17

SP - 1043

EP - 1053

JO - EXCLI Journal

JF - EXCLI Journal

SN - 1611-2156

ER -

ID: 215508855