title: Isoniazid-induced polyneuropathy in a tuberculosis patient - implication for individual risk stratification with genotyping?
abstract: BACKGROUND
  Development of polyneuropathy (PNP) under treatment for tuberculosis (TB), including isoniazid (INH), is a highly relevant adverse drug effect. The NAT2 acetylation status is a predictor of potential toxic effects of INH. The question as to whether individual risk stratification by genotyping is useful to avoid suffering of patients and to lower costs for the health care system is of considerable clinical importance.
  
  
  METHODS
  After drug treatment for TB, including INH, a 23-year-old man developed severe PNP. During the treatment, laboratory results have been indicating incipient liver and renal injury. Later, molecular genetic analyses were performed and revealed a variation in the NAT2 gene and the c1/c2 genotype of the CYP2E1 gene, both described to contribute to an elevated risk for anti-tuberculostatic-induced liver damages (ATIL).
  
  
  CONCLUSIONS
  The combination of metabolizer genotypes should be taken into account as a cause for toxic effects and the development of PNP. Individual genotyping, performed before medication or at least if an elevation of liver parameters is observed, may reduce the risk of severe cases of PNP by early adjustment of treatment. Our case study indicates that evaluation of individual risk stratification with systematic pharmacogenetic genotyping of metabolizer gene combinations in the context of TB treatment should be addressed in clinical studies with larger cohorts.
authors.affiliation: Department of Neurology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Stettner
authors.affiliation: bio.logis Center for Human Genetics, Frankfurter Innovationszentrum Biotechnologie (FIZ) Frankfurt am Main, Germany ; Institute of Human Genetics, Justus-Liebig-University Giessen, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Steinberger
authors.affiliation: Department of Neurology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Germany.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Hartmann
authors.affiliation: bio.logis Center for Human Genetics, Frankfurter Innovationszentrum Biotechnologie (FIZ) Frankfurt am Main, Germany.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Pabst
authors.affiliation: bio.logis Center for Human Genetics, Frankfurter Innovationszentrum Biotechnologie (FIZ) Frankfurt am Main, Germany.
authors.forename: Lidija
authors.initials: L
authors.lastname: Konta
authors.affiliation: Department of Neurology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Germany.
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Hartung
authors.affiliation: Department of Neurology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Germany.
authors.forename: Bernd C
authors.initials: BC
authors.lastname: Kieseier
mesh_terms: D000328:Adult; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D056726:Genetic Association Studies; D006801:Humans; D007538:Isoniazid / Q000009:adverse effects*; D008297:Male; D011110:Polymorphism, Genetic; D011115:Polyneuropathies / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D012307:Risk Factors; D014376:Tuberculosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D007538:Isoniazid
keywords: CYP2E1; N-acetyltransferase 2; NAT2; c1/c2; individual risk stratification; isoniazid; linezolid; polyneuropathy; side effects; slow acetylators; toxic effects; tuberculosis