Study of correlation between the NAT2 phenotype and genotype status among Greenlandic Inuit

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dc.contributor.authorBirch Kristensen, Emilie
dc.contributor.authorYakimov, Victor
dc.contributor.authorBjorn-Mortensen, Karen
dc.contributor.authorSoborg, Bolette
dc.contributor.authorKoch, Anders
dc.contributor.authorAndersson, Mikael
dc.contributor.authorBirch Kristensen, Kasper
dc.contributor.authorMichelsen, Sascha Wilk
dc.contributor.authorSkotte, Line
dc.contributor.authorAhrendt Bjerregaard, Anne
dc.contributor.authorBlaszkewicz, Meinolf
dc.contributor.authorGolka, Klaus
dc.contributor.authorHengstler, Jan G.
dc.contributor.authorFeenstra, Bjarke
dc.contributor.authorMelbye, Mads
dc.contributor.authorGeller, Frank
dc.date.accessioned2019-04-02T06:15:55Z
dc.date.available2019-04-02T06:15:55Z
dc.date.issued2018-11-02
dc.description.abstractN-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.en
dc.identifier.issn1611-2156
dc.identifier.urihttp://hdl.handle.net/2003/37972
dc.identifier.urihttp://dx.doi.org/10.17877/DE290R-19957
dc.language.isoen
dc.relation.ispartofseriesEXCLI Journal;Vol. 17 2018
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectN-acetyltransferase 2en
dc.subjectGreenlanden
dc.subjectNAT2 genotype statusen
dc.subjectNAT2 enzyme activityen
dc.subjectCaffeine testen
dc.subjectIsoniaziden
dc.subject.ddc610
dc.titleStudy of correlation between the NAT2 phenotype and genotype status among Greenlandic Inuiten
dc.typeText
dc.type.publicationtypearticle
dcterms.accessRightsopen access
eldorado.dnb.zdberstkatid2132560-1
eldorado.secondarypublicationtrue

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