Skip to main content
SpringerLink
Log in

The influence of various genotypes on the metabolic activity of NAT2 in a Chinese population

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Aim

To determine the phenotype and genotype of NAT2 in a Chinese population and study the influence of various NAT2 genotypes on the NAT2 activity.

Methods

A reverse dot blot method was used to detect the genotype of NAT2 in 120 healthy Chinese subjects. All subjects were given a single dose of 500 mg sulphadimidine (SM2). The plasma concentration of SM2 and acetyl-SM2 (AcSM2) 6 h after administration was determined. Molar metabolic ratio (MR) was calculated by the ratio of AcSM2 to AcSM2+SM2.

Results

Totals of 53 (44.2%), 47 (39.2%) and 20 (16.7%) subjects were homozygotes for wild type (wt/wt), heterozygotes for mutant (m/wt) and homozygotes for mutant (m/m), respectively. The MR of 120 subjects was 0.714±0.237. Twenty subjects (16.7%) were classified as poor metabolizers. All subjects in the m/m group were poor metabolizers. The MRs of the wt/wt, m/wt and m/m groups were 0.886±0.060, 0.719±0.089 and 0.246±0.105 (P<0.001), respectively. There was a significant difference between different NAT2 m/wt genotypes (P<0.001) and m/m genotypes (P<0.001). MR correlated well with NAT2 genotypes (r=0.947).

Conclusion

Various NAT2 genotypes have a significant impact on the metabolic activity of NAT2 in Chinese people.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Evans DA (1989) N-acetyltransferase. Pharmacol Ther 42:157–234

    Article  PubMed  CAS  Google Scholar 

  2. Rey E, Pons G, Cremier O et al (1998) Isoniazid dose adjustment in a pediatric population. Ther Drug Monit 20:50–55

    Article  PubMed  CAS  Google Scholar 

  3. Hiratsuka M, Kishikawa Y, Takekuma Y, et al (2002) Genotyping of the N-acetyltransferase2 polymorphism in the prediction of adverse drug reactions to isoniazid in Japanese patients. Drug Metab Pharmacokinet 17:357–362

    Article  PubMed  CAS  Google Scholar 

  4. Deguchi T, Mashimo M, Suzuki T (1990) Correlation between acetylator phenotypes and genotypes of polymorphic arylamine N-acetyltransferase in human liver. J Biol Chem 265:12757–12760

    PubMed  CAS  Google Scholar 

  5. Mashimo M, Suzuki T, Abe M, Duguchi T (1992) Molecular genotyping of N-acetylation polymorphism to predict phenotype. Hum Genet 90:139–143

    Article  PubMed  CAS  Google Scholar 

  6. Hein DW, Ferguson RJ, Doll MA, Rustan TD, Gray K (1994) Molecular genetics of human polymorphic N-acetyltransferase: enzymatic analysis of 15 recombinant wild-type, mutant, and chimeric NAT2 allozymes. Hum Mol Genet 3(5):729–734

    Article  PubMed  CAS  Google Scholar 

  7. Agundez JA, Olivera M, Martinez C, Ladero JM, Benitez J (1996) Identification and prevalence study of 17 allelic variants of the human NAT2 gene in a white population. Pharmacogenetics 6:423–428

    Article  PubMed  CAS  Google Scholar 

  8. Lin HJ, Han CY, Lin BK, Hardy S (1993) Slow acetylator mutations in the human polymorphic N-acetyltransferase gene in 786 Asians, blacks, Hispanics, and whites: application to metabolic epidemiology. Am J Hum Genet 52:827–834

    PubMed  CAS  Google Scholar 

  9. Xie HG, Xu ZH, OuYang DS, Shu Y, Yang DL, Wang JS, Yan XD, Huang SL, Wang W, Zhou HH (1997) Meta-analysis of phenotype and genotype of NAT2 deficiency in Chinese populations. Pharmacogenetics 7:503–514

    Article  PubMed  CAS  Google Scholar 

  10. Hein DW, Doll MA, Rustan TD, Ferguson RJ (1995) Metabolic activation of N-hydroxyarylamines and N-hydroxyarylamides by 16 recombinant human NAT2 allozymes: effects of 7 specific NAT2 nucleic acid substitutions. Cancer Res 55:3531–3536

    PubMed  CAS  Google Scholar 

  11. Kinzig-Schippers M, Tomalik-Scharte D, Jetter A, Scheidel B, Jakob V, Rodamer M, et al (2005) Should we use N-acetyltransferase type 2 genotyping to personalize isoniazid doses? Antimicrob Agents Chemother. 49:1733–1738

    Article  PubMed  CAS  Google Scholar 

  12. Chen B, Li JH (2004) A reverse dot blot method for genotyping of NAT2 in Chinese subjects Chin Pharmacol Bull 20:1269–1272

    CAS  Google Scholar 

  13. Lu JF, Zhou XD, Zhu XP, Cao XM, Guo LQ, Lin SS (1997) N-acetyltransferase phenoytpe in 120 Chinese using sulfamethazine as the probe drug. Chin Pharm J 32:559–561

    CAS  Google Scholar 

  14. Vistisen K, Poulsen HE, Loft S (1992) Foreign compound metabolism capacity in man measured from metabolites of dietary caffeine. Carcinogenesis 13:1561–1568

    Article  PubMed  CAS  Google Scholar 

  15. Xu XM, Jiang WD (1990) Debrisoquine hydroxylation and sulfamethazine acetylation in a Chinese population. Acta Pharmacologica Sinica 11:385–388

    PubMed  CAS  Google Scholar 

  16. Smith CA, Wadelius M, Gough AC, Harrison DJ, Wolf CR, Rane A (1997) A simplified assay for the arylamine N-acetyltransferase 2 polymorphism validated by phenotyping with isoniazid. J Med Genet 34:758–760

    Article  PubMed  CAS  Google Scholar 

  17. Gross M, Kruisselbrink T, Anderson K, Lang N, McGovern P, Delongchamp R, Kadlubar F (1999) Distribution and concordance of N-acetyltransferase genotype and phenotype in an American population. Cancer Epidemiol Biomarkers Prev 8:683–692

    PubMed  CAS  Google Scholar 

  18. Rothman N, Hayes RB, Bi W, Caporaso N, Broly F, Woosley RL, Yin S, Feng P, You X, Meyer UA (1993) Correlation between N-acetyltransferase activity and NAT2 genotype in Chinese males. Pharmacogenetics 3:250–255

    Article  PubMed  CAS  Google Scholar 

  19. Zhao B, Seow A, Lee EJ, Lee HP (2000) Correlation between acetylation phenotype and genotype in Chinese women. Eur J Clin Pharmacol 56:689–692

    Article  PubMed  CAS  Google Scholar 

  20. Meisel P, Arndt D, Scheuch E, Klebingat KJ, Siegmund W (2001) Prediction of metabolic activity from genotype: the gene-dose effect of N-acetyltransferase. Ther Drug Monit 23:9–14

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacy, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200025, People’s Republic of China

    Bing Chen, Wei-Xia Zhang & Wei-Min Cai

Authors
  1. Bing Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wei-Xia Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wei-Min Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wei-Min Cai.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, B., Zhang, WX. & Cai, WM. The influence of various genotypes on the metabolic activity of NAT2 in a Chinese population. Eur J Clin Pharmacol 62, 355–359 (2006). https://doi.org/10.1007/s00228-006-0110-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-006-0110-6

Keywords

Search

Navigation