| Title | Genetic polymorphism of the metabolic enzymes CYP1A2, CYP2A6 and NAT-2 in the Greek population: impact of NAT-2 polymorphism in tuberculosis treatment | |
| Authors | K. Balaskonis¹, E. Malliara¹, S. Bauer², S. Markantonis-Kyroudis¹, A. Papavasiliou³ and N. Drakoulis¹
1. University of Athens, School of Pharmacy, Greece 2. Charite University Medicine Berlin, Germany 3. Sotiria General Hospital, Athens, Greece |
|
| Citation | Balaskonis, K., Malliara, G., Bauer, S., Markantonis-Kyroudis, S., Papavasiliou, A. et al: Genetic polymorphism of the metabolic enzymes CYP1A2, CYP2A6 and NAT-2 in the Greek population: impact of NAT-2 polymorphism in tuberculosis treatment, Epitheorese Klin. Farmakol. Farmakokinet. 20(2): 75-77 (2006) | |
| Publication Date | Accepted for publication: 19-20 May 2006 | |
| Full Text Language | English | |
| Order – Buy | Ηλεκτρονική Μορφή: pdf (10 €) – Digital Type: pdf (10 €)
pharmakonpress[at]pharmakonpress[.]gr |
|
| Keywords | NAT2, CYP2A6, polymorphism, tuberculosis, isoniazid, hepatotoxicity. | |
| Other Terms | review article | |
| Summary | The aim of this study was to assess i) genetic polymorphism of the hepatic metabolic enzymes CYP1A2, CYP2A6 and NAT-2 in the Greek population, and ii) the impact of acetylator status on the therapeutic response to antimycobacterial agents, as well as on the hepatotoxic effect of isoniazid. The phenotyping method used for the assessment of the catalytic activity of the 3 enzymes was that described by Grant et al. The control group comprised 193 healthy volunteers (93 men and 100 women, mean-age 41 years), while the group under antituberculotic treatment comprised 49 volunteers (32 men and 17 women, mean-age 54 years). The results indicated that the majority of the Greek population may be characterized as CYP2A6 Extensive Metabolizers (EM). Also a correlation between CYP2A6 PM phenotype and non- smoking habits may exist (OR=0,27, CL 0,09-0,82, p=0,03). No such correlation was found between catalytic activity of CYP2A6 and gender. The theoretical induction of CYP2A6 by rifampicin was not confirmed. The majority of the Greek population may also be characterized as fast acetylators. A correlation between smoking and decreased NAT-2 catalytic activity was found (OR=2,02, CL 1,09- 3,77, p=0,037) but not between gender and acetylator status. No impact of acetylator status on therapeutic response to the antimycobacterial agents was observed, but the importance of fast acetylator phenotype as a major risk factor for hepatotoxicity due to isoniazid, was confirmed (OR=2,75, CL 0,52-14,44, p=0,297). The importance of old age, female gender and poor nutritional status as risk factors for isoniazid induced hepatotoxicity needs further study as does the existence of CYP1A2 polymorphism in the Greek population. | |
| References | 1. Glue P., Banfield C.: Psychiatry, Psychopharmacology and P450s. Human Psycopharmacology 11: 97-114 (1996)
2. Chun.Xu, Goodz S, Edward M, Sellers M and Tyndale R F. (2002) CYP2A6 genetic variation and potential sequences. Advanced Drug Delivery Reviews, 54, 1245-1256 (1996) 3. Grant D.M., Tang B.K., Kalow W.: A simple test for acetylator phenotype using caffeine. Br. J. Clin. Pharmacol. 17: 459- 464 (1984) 4. Grant D.M., Tang B.K., Kalow W.: Polymorphic acetylation of a caffeine metabolite. Clin. Pharmacol. Ther. 33: 355-359 (1983) 5. Grant D.M., Tang B.K., Kalow W.: Variability in caffeine metabolism. Clin. Pharmacol. Ther. 33: 599-602 (1983) |
|
| Relative Papers |
Online ISSN 1011-6575
Άρθρα Δημοσιευμένα σε αυτό το Περιοδικό Καταχωρούνται στα:
- Chemical Abstracts
- Elsevier’s Bibliographic Databases: Scopus, EMBASE, EMBiology, Elsevier BIOBASE SCImago Journal and Country Rank Factor
Articles published in this Journal are Indexed or Abstracted in: • Chemical Abstracts • Elsevier’s Bibliographic Databases: Scopus, EMBASE, EMBiology, Elsevier BIOBASE SCImago Journal and Country Rank Factor
Συντακτικη Επιτροπή-Editorial Board
| ΕΤΗΣΙΑ ΣΥΝΔΡΟΜΗ 2006 – ANNUAL SUBSCRIPTION 2006 | |
| Γλώσσα Πλήρους Κειμένου – Full Text Language | Αγγλικά – English |
| Παραγγελία – Αγορά – Order – Buy | Ηλεκτρονική Μορφή: pdf (70 €) – Digital Type: pdf (70 €)
pharmakonpress[at]pharmakonpress[.]gr |
| Έντυπη Μορφή (70 € + έξοδα αποστολής) – Printed Type (70 € + shipping)
pharmakonpress[at]pharmakonpress[.]gr |
|