Research Article

Human genetic variation of CYP450 superfamily: analysis of functional diversity in worldwide populations

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Department of Biology, University of Rome, “Tor Vergata”, Via della Ricerca Scientifica 1, 00133, Rome, Italy.

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Email the corresponding author at renatopolimanti@alice.it

Sara Piacentini

Department of Biology, University of Rome, “Tor Vergata”, Via della Ricerca Scientifica 1, 00133, Rome, Italy

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Dario Manfellotto

Clinical Pathophysiology Center, “San Giovanni Calibita” Fatebenefratelli Hospital – Associazione Fatebenefratelli per la Ricerca, Isola Tiberina, Rome, Italy

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Maria Fuciarelli

Department of Biology, University of Rome, “Tor Vergata”, Via della Ricerca Scientifica 1, 00133, Rome, Italy

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Published Online:10 Dec 2012https://doi.org/10.2217/pgs.12.163

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Abstract

Aim: The present study aimed to investigate the human genetic diversity of the CYP450 superfamily in order to identify functional interethnic differences and analyze the role of CYP450 enzymes in human adaptation. Materials & methods: A computational analysis of genetic and functional differences of the 57 CYP450 genes was performed using the Human Genome Diversity Project and HapMap data; comprising approximately 1694 individuals belonging to 62 human populations. Results: Twenty-six CYP450 SNPs with F-statistics significantly different than the general distribution were identified. Some showed high differentiation among human populations, suggesting that functional interethnic differences may be present. Indeed, some of these are significantly associated with drug response or disease risk. Furthermore, our data highlighted that TBXAS1 and genes in CYP3A cluster may have a role in some processes of human adaptation. Conclusion: Our study provided an analysis of genetic diversity of CYP450 superfamily, identifying functional differences among ethnic groups and their related clinical phenotypes.

Original submitted 18 July 2012; Revision submitted 21 September 2012

Keywords:

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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Acknowledgements

Thanks to A Novelletto (University of Rome ‘Tor Vergata’) for stimulating discussions on the subject. The authors are grateful to the research groups of the HapMap Consortium and of the Human Genome Diversity Project for their essential contributions.

Financial & competing interests disclosure

This work was supported by the RSA Grant 2009 –University of Rome ‘Tor Vergata’ to M Fuciarelli and by the PRIN 2009 grant (prot. n. 200975T9EW). 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.

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