nach oben

Molecular Diagnosis & Therapy

Erschienen in:

01.03.2009 | Original Research Article

Study of NAT2 Gene Polymorphisms in an Indian Population

Association with Plasma Isoniazid Concentration in a Cohort of Tuberculosis Patients

verfasst von: Neera Singh, Sudhisha Dubey, Saravanan Chinnaraj, Anil Golani, Dr Anurupa Maitra

Erschienen in: Molecular Diagnosis & Therapy | Ausgabe 1/2009

Einloggen, um Zugang zu erhalten

Abstract

Methods: NAT2 genotyping of 201 subjects was carried out by PCR-restriction fragment length polymorphism (PCR-RFLP) analysis and DNA sequencing. Acetylation phenotypes were predicted from NAT2 genotypes. The association of au]|NAT2 genotypes with plasma isoniazid concentrations was determined by measuring the plasma levels in tuberculosis patients at different time points using reverse-phase high-performance liquid chromatography (HPLC).

Results: The predominant alleles found in this study population were NAT2*5B and NAT2*6A, while NAT2*5B/*6A and NAT2*6A/*6A were the most frequent genotypes; the frequency varied widely from other reported studies in the Indian population. The distribution of slow, intermediate, and fast acetylators was 55%, 32%, and 13%, respectively. We observed relatively higher plasma concentrations of isoniazid in our patients than those reported in other similar studies, and they correlated well with the au]|NAT2 genotypes.

Conclusion: The results suggested high variation in the frequencies of au]|NAT2 alleles and genotypes within Indian populations, which influence plasma isoniazid concentrations. Further studies of the relationship between NAT2 genotypes and adverse drug events are required to make genotyping a helpful tool for optimizing the isoniazid therapeutic response and minimizing adverse drug reactions, particularly in countries with a high burden of tuberculosis.

Hughes HB, Biehl JP, Jones AP, et al. Metabolism of isoniazid in man as related to the occurrence of peripheral neuritis. Am Rev Tuberc 1954; 70: 266–73PubMed

Evans DA, Manley KA, Mckuscik VA. Genetic control of isoniazid metabolism in man. Br Med J 1960; 2: 485–91PubMedCrossRef

Hirvonen A. Polymorphic NATs and cancer predisposition. IARC Sci Publ 1999; 148: 251–70PubMed

Pawlik A, Ostanek L, Brzosko I, et al. Increased genotype frequency of N-acetyltransferase 2 slow acetylation in patients with rheumatoid arthritis. Clin Pharmacol Ther 2002; 72: 319–25PubMedCrossRef

Chaudhary S, Behari M, Dihana M, et al. Association of N-acetyl transferase 2 gene polymorphism and slow acetylator phenotype with young onset and late onset Parkinson’s disease among Indians. Pharmacogenet Genomics 2005; 15:731–75PubMedCrossRef

Machida H, Tsukamoto K, Wen CY, et al. Crohn’s disease in Japanese is associated with a SNP-haplotype of N-acetyltransferase 2 gene. World J Gastroenterol 2005; 11: 4833–7PubMed

Kubota R, Ohno M, Hasunuma T, et al. Dose-escalation study of isoniazid in healthy volunteers with the rapid acetylator genotype of arylamine N-acetyltransferase 2. Eur J Clin Pharmacol 2007; 63: 927–33PubMedCrossRef

WHO. Global tuberculosis control: surveillance, planning, financing. WHO report no. WHO/HTM/TB/2008.393. Geneva: WHO, 2008 [online]. Available from URL: http://www.who.int/tb/publications/global_report/2008/pdf/fullreport.pdf [Accessed 2008 Feb 19]

Steinbrook R. ai]Tuberculosis_and HIV in India. N Engl J Med 2007; 356: 1198–9PubMedCrossRef

10.

Hiratsuka M, Kishikawa Y, Takekuma Y, et al. Genotyping of the N-acetyltransferase2 polymorphism in the prediction of adverse drug reactions to isoniazid in Japanese patients. Drug Metab Pharmacokinet 2002; 17: 357–62PubMedCrossRef

11.

Weinshilboum R. Inheritance and drug response. N Engl J Med 2003; 348: 529–37PubMedCrossRef

12.

Suzuki H, Morris JS, Li Y, et al. Interaction of the cytochrome P4501A2, SULT1 A1 and NAT gene polymorphisms with smoking and dietary mutagen intake in modification of the risk of pancreatic cancer. Carcinogenesis 2008; 29: 1184–91PubMedCrossRef

13.

Parkin DP, Vandenplas S, Botha FJ, et al. Trimodality of isoniazid elimination: phenotype and genotype in patients with tuberculosis. Am J Respir Crit Care Med 1997; 155: 1717–22PubMed

14.

Cascorbi I, Brockmöller J, Bauer S, et al. NAT2*12A (803AG) codes for rapid arylamine N-acetylation in humans. Pharmacogenetics 1996; 6: 257–9PubMedCrossRef

15.

Hein DW. Human au] NAT2 alleles [online]. Available from URL: http://N-acetyltransferasenomenclature.louisville.edu [Accessed 2008 Jan 22]

16.

Garte S, Gaspari L, Alexandrie AK, et al. Metabolic gene polymorphism frequencies in control populations. Cancer Epidemiol Biomarkers Prev 2001; 10: 1239–48PubMed

17.

Patin E, Barreiro LB, Sabeti PC, et al. Deciphering the ancient and complex evolutionary history of human arylamine N-acetyltransferase genes. Am J Hum Genet 2006; 78: 423–36PubMedCrossRef

18.

Butcher NJ, Boukouvala S, Sim E, et al. Pharmacogenetics of the arylamine N-acetyltransferases. Pharmacogenomics J 2002; 2: 30–42PubMedCrossRef

19.

Lee SY, Lee KA, Ki CS, et al. Complete sequencing of a genetic polymorphism in NAT2 in the Korean population. Clin Chem 2002; 48: 775–7PubMed

20.

Jain M, Kumar S, Lal P, et al. Association of genetic polymorphisms of N-acetyltransferase 2 and susceptibility to esophageal cancer in north Indian population. Cancer Invest 2007; 25: 340–6PubMedCrossRef

21.

Mittal RD, Srivastava DS, Mandhani A. NAT2 gene polymorphism in bladder cancer: a study from North India. Int Braz J Urol 2004; 30: 279–85PubMedCrossRef

22.

Srivastava DS, Mittal RD. Genetic polymorphism of the N-acetyltransferase 2 gene, and susceptibility to prostate cancer: a pilot study in north Indian population. BMC Urol 2005; 5: 12PubMedCrossRef

23.

Arif E, Vibhuti A, Alam P, et al. Association of CYP2E1 and NAT2 gene polymorphisms with chronic obstructive pulmonary disease. Clin Chim Acta 2007; 382: 37–42PubMedCrossRef

24.

Babu KA, Rao KL, Reddy NG, et al. N-acetyl transferase 2 polymorphism and advanced stages of endometriosis in South Indian women. Reprod Biomed Online 2004; 9: 533–40PubMedCrossRef

25.

Anitha A, Banerjee M. Arylamine N-acetyltransferase 2 polymorphism in the ethnic populations of south India. Int J Mol Med 2003; 11: 125–31PubMed

26.

Doll MA, Fretland JF, Deitz AC, et al. Determination of human NAT2 acetylator genotype by restriction fragment length polymorphism and allele-specific amplification. Analyt Biochem 1995; 231: 413–20PubMedCrossRef

27.

Singh N, Golani A, Patel Z, et al. Transfer of isoniazid from circulation to breast milk in lactating women on chronic therapy for tuberculosis. Br J Clin Pharmacol 2008; 65: 418–22PubMedCrossRef

28.

Thomann P. Non-compartmental analysis methods manual. In: Heinzel G, Woloszcak R, Thomann P, editors. TopFit 2.0 pharmacokinetic and pharmacodynamic data analysis system for the PC. Stuttgart: Gustav Fischer, 1993: 5–66

29.

Stephens M, Donnelly P. A comparison of bayesian methods for haplotype reconstruction from population genotype data. Am J Hum Genet 2003; 5: 1162–9CrossRef

30.

HAP-Haplotype analysis tool [online]. Available from URL: http://research.calit2.net/hap/WebServer.htm [Accessed 2008 Nov 14]

31.

Barrett JC, Fry B, Maller J, et al. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005; 21: 263–5PubMedCrossRef

32.

Rychlik-Sych M, Skretkowicz J, Gawroñska-Szklarz B, et al. Acetylation genotype and phenotype in patients with systemic lupus erythematosus. Pharmacol Rep 2006; 58: 22–9PubMed

33.

Tanigawara Y, Kita T, Aoyama N, et al. N-acetyltransferase 2 genotype-related sulfapyridine acetylation and its adverse events. Biol Pharm Bull 2002; 25: 1058–62PubMedCrossRef

34.

Grant DM, Tang BK, Kalow W. A simple test for acetylator phenotype using caffeine. Br J Clin Pharmacol 1984; 17: 459–64PubMedCrossRef

35.

Morton LM, Schenk M, Hein DW, et al. Genetic variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2) and risk of non-Hodgkin lymphoma. Pharmacogenet Genomics 2006; 16: 537–45PubMedCrossRef

36.

Bu R, Gutiérrez MI, Al-Rasheed M, et al. Variable drug metabolism genes in Arab population. Pharmacogenomics J 2004; 4: 260–6PubMedCrossRef

37.

Loktionov A, Moore W, Spencer SP, et al. Differences in N-acetylation genotypes between Caucasians and Black South Africans: implications for cancer prevention. Cancer Detect Prev 2002; 26: 15–22PubMedCrossRef

38.

Chen B, Li JH, Xu YM, et al. The influence of NAT2 genotypes on the plasma concentration of isoniazid and acetylisoniazid in Chinese pulmonary tuberculosis patients. Clin Chim Acta 2006; 365: 104–8PubMedCrossRef

39.

Yuliwulandari R, Sachrowardi Q, Nishida N, et al. Polymorphisms of promoter and coding regions of the arylamine N-acetyltransferase 2 (NAT2) gene in the Indonesian population: proposal for a new nomenclature. J Hum Genet 2008; 53: 201–9PubMedCrossRef

40.

Kukongviriyapan V, Prawan A, Tassaneyakul W, et al. Arylamine N-acetyltransferase-2 genotypes in the Thai population. Br J Clin Pharmacol 2003; 55: 278–81PubMedCrossRef

41.

Torkaman-Boutorabi A, Hoormand M, Naghdi N, et al. Genotype and allele frequencies of N-acetyltransferase 2 and glutathione S-transferase in the Iranian population. Clin Exp Pharmacol Physiol 2007; 34: 1207–11PubMedCrossRef

42.

Schnakenberg E, Ehlers C, Feyerabend W, et al. Genotyping of the polymorphic N-acetyltransferase (NAT2) and loss of heterozygosity in bladder cancer patients. Clin Genet 1998; 53: 396–402PubMedCrossRef

43.

Ellard GA. Variations between individuals and populations in the acetylation of isoniazid and its significance for the treatment of pulmonary tuberculosis. Clin Pharmacol Ther 1976; 19: 610–25PubMed

44.

Kinzig-Schippers M, Tomalik-Scharte D, Jetter A, et al. Should we use N-acetyltransferase type 2 genotyping to personalize isoniazid doses? Antimicrob Agents Chemother 2005; 49: 1733–8PubMedCrossRef

45.

Huang YS, Chern HD, Su WJ, et al. Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug-induced hepatitis. Hepatology 2002; 35: 883–9PubMedCrossRef

46.

Yew WW. Therapeutic drug monitoring in antituberculosis chemotherapy. Ther Drug Mon 1998; 20: 469–72CrossRef

47.

Meyers FH, Jawetz E, Goldfien A. Review of medical pharmacology, 5th ed. Los Altos (CA): Lange Medical Publications, 1976

48.

Schaaf HS, Parkin DP, Seifart HI, et al. Isoniazid pharmacokinetics in children treated for respiratory tuberculosis. Arch Dis Child 2005; 90: 551–3CrossRef

49.

Conte Jr JE, Golden JA, McQuitty M, et al. Effects of gender, AIDS, and acetylator status on intrapulmonary concentrations of isoniazid. Antimicrob Agents Chemother 2002; 46: 2358–64PubMedCrossRef

50.

Possuelo LG, Castelan JA, de Brito TC, et al. Association of slow N-acetyltransferase 2 profile and anti-TB drug-induced hepatotoxicity in patients from Southern Brazil. Eur J Clin Pharmacol 2008; 64: 673–81PubMedCrossRef

Titel: Study of NAT2 Gene Polymorphisms in an Indian Population
Association with Plasma Isoniazid Concentration in a Cohort of Tuberculosis Patients
verfasst von: Neera Singh
Sudhisha Dubey
Saravanan Chinnaraj
Anil Golani
Dr Anurupa Maitra
Publikationsdatum: 01.03.2009
Verlag: Springer International Publishing
Erschienen in: Molecular Diagnosis & Therapy / Ausgabe 1/2009
Print ISSN: 1177-1062
Elektronische ISSN: 1179-2000
DOI: https://doi.org/10.1007/BF03256314

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

„Überwältigende“ Evidenz für Tripeltherapie beim metastasierten Prostata-Ca.

22.05.2024 Prostatakarzinom Nachrichten

Patienten mit metastasiertem hormonsensitivem Prostatakarzinom sollten nicht mehr mit einer alleinigen Androgendeprivationstherapie (ADT) behandelt werden, mahnt ein US-Team nach Sichtung der aktuellen Datenlage. Mit einer Tripeltherapie haben die Betroffenen offenbar die besten Überlebenschancen.

So sicher sind Tattoos: Neue Daten zur Risikobewertung

22.05.2024 Melanom Nachrichten

Das größte medizinische Problem bei Tattoos bleiben allergische Reaktionen. Melanome werden dadurch offensichtlich nicht gefördert, die Farbpigmente könnten aber andere Tumoren begünstigen.

CAR-M-Zellen: Warten auf das große Fressen

22.05.2024 Onkologische Immuntherapie Nachrichten

Auch myeloide Immunzellen lassen sich mit chimären Antigenrezeptoren gegen Tumoren ausstatten. Solche CAR-Fresszell-Therapien werden jetzt für solide Tumoren entwickelt. Künftig soll dieser Prozess nicht mehr ex vivo, sondern per mRNA im Körper der Betroffenen erfolgen.

Frühzeitige HbA1c-Kontrolle macht sich lebenslang bemerkbar

22.05.2024 Typ-2-Diabetes Nachrichten

Menschen mit Typ-2-Diabetes von Anfang an intensiv BZ-senkend zu behandeln, wirkt sich positiv auf Komplikationen und Mortalität aus – und das offenbar lebenslang, wie eine weitere Nachfolgeuntersuchung der UKPD-Studie nahelegt.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2009

From the Literature

HIV-1 with Predicted CXCR4 Genotype Identified in Clade C from India

Development and Validation of a High-Throughput Screening Method for Two Polymorphisms in the Serotonin Transporter Gene

3M™ Rapid Detection Flu A + B Test

Cost Effectiveness of Risk-Prediction Tools in SelectingPatients for Immediate Post-Prostatectomy Treatment

Previstage™ GCC Colorectal Cancer Staging Test