N-acetyltransferase 2 (NAT2) is a well-studied phase II xenobiotic metabolizing enzyme relevant in drug metabolism and cancerogenesis. NAT2 activity is largely determined by genetic polymorphisms in the coding region of the corresponding gene. We investigated NAT2 acetylation status in 1556 individuals from Greenland based on four different single nucleotide polymorphism (SNP) panels and the tagging SNP rs1495741. There was good concordance between the NAT2 status inferred by the different SNP combinations. Overall, the fraction of slow acetylators was low with 17.5 % and varied depending on the degree of Inuit ancestry; in individuals with <50 % Inuit ancestry, we observed more than 25 % slow acetylators reflecting European ancestry. Greenland has a high incidence of tuberculosis, and individual dosing of isoniazid according to NAT2 status has been shown to improve treatment and reduce side effects. Our findings could be a first step in pharmacogenetics-based tuberculosis therapy in Greenland.

BackgroundThe incidence of tuberculosis (TB) disease in Greenland doubled in the 1990s. To combat the increase, national TB interventions were initiated in 2000 and strengthened in 2007.ObjectiveTo determine whether the effect of interventions could be detected, we estimated the TB disease risk among children≤15 years before and after interventions were implemented.DesignFor a study cohort, we recruited all children ≤15 years of age included in the Greenlandic Civil Registration System (CRS) from 1990 to 2010. The CRS identifier was used to link cohort participants with TB cases identified based on the Greenlandic National TB registry. Bacille Calmette Guerin (BCG) vaccination status was identified through year of birth, as BCG was offered to newborns born either before 1991 or after 1996. Years with interventions were defined as 2000–2006 (primary interventions) and 2007–2010 (intensified interventions). Risk of TB was estimated using Poisson regression.ResultsThe study included 35,858 children, of whom 209 had TB disease. The TB disease incidence decreased after interventions were implemented (2007–2010: IRR [incidence rate ratios] 0.62, 95% CI: 0.39–0.95, p=0.03, compared with the 1995–1999 period). The TB disease risk was inversely associated with BCG vaccination (IRR: 0.54, 95% CI: 0.41–0.72, p<0.001).ConclusionsYears with national TB interventions in Greenland, including neonate BCG vaccination, are associated with a lower TB disease incidence among children ≤15 years of age.