NAT2 Sequence Polymorphisms and Acetylation ProFiles in Indians

Abstract

Background: NAT2, a broad-spectrum drug-metabolizing gene, is of high pharmacogenetic interest. Based on seven different mutations in the NAT2 gene, an individual can either be categorized as a slow or fast acetylator. Materials & methods: In order to characterize acetylation profiles of Indians, where data are poorly available, we sequenced the 873 bp NAT2 coding region in 250 Indians, covering the whole of India including three tribes. Results: Altogether, 35 NAT2 alleles forming two acetylator phenotypes (distributed almost in equal proportion in India) were found; while the alleles determining slow acetylators were highly differentiated, the fast acetylator alleles were less in number but highly frequent. Conclusion: Interestingly, distribution of two different acetylation phenotypes correlated well with historical dietary pattern in India. The neighbor-joining phylogenetic tree based on NAT2 gene polymorphisms in worldwide humans revealed genetic affinities among populations with similar acetylation phenotypes, which also placed Indians and Africans together in a single cluster.

Original submitted 22 August 2012; Revision submitted 1 January 2013

KEYWORDS::

• acetylation phenotypes
• drug metabolization
• India
• N-acetyltransferase 2
• NAT2
• pharmacogenetic

Acknowledgements

The authors are highly thankful to all blood donors of the present study and AP Dash, former Director, and N Valecha, present Director, National Institute of Malaria Research (NIMR) for support and encouragement. The authors thank ES Poloni, University of Geneva, Switzerland, for valuable suggestions at different stages of the work and MR Ranjit for his help in sampling the tribal samples from Odisha, India. Critical and constitutive comments from the anonymous reviewers on an earlier version of the manuscript have helped in substantially improving the final manuscript.

Financial & competing interests disclosure

N Khan thanks the Indian Council of Medical Research (ICMR) for Junior and Senior Research Fellowships. A Das thanks the Indian Council of Medical Research (ICMR), New Delhi for intramural funding. This paper bears the NIMR publication screening committee approval number 039/2012. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

N Khan thanks the Indian Council of Medical Research (ICMR) for Junior and Senior Research Fellowships. A Das thanks the Indian Council of Medical Research (ICMR), New Delhi for intramural funding. This paper bears the NIMR publication screening committee approval number 039/2012. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart rom those disclosed. No writing assistance was utilized in the production of this manuscript.