Functional Diversity of the Glutathione Peroxidase Gene Family Among Human Populations: Implications for Genetic Predisposition to Disease and Drug Response

Abstract

Aim: To analyze the human genetic variation of glutathione peroxidases (GPX), estimating the functional differences among human populations and suggesting interethnic differences in predisposition to disease and drug response. Materials & methods: Using 1000 Genomes Project data, we analyzed 723 GPX variants in 1092 individuals belonging to 14 populations. Combining functional prediction analyses of coding and noncoding variants, we developed a method to estimate haplotype functionality. Results: GPX rare variants have a higher functional impact than common variants. The frequency among Asian patients of haplotypes associated with normal functionality is significantly higher for GPX1 and lower for GPX3 than for non-Asian patients; no adaptation signals in GPX1 and GPX3 were found in Asian patients. Conclusion: GPX1 and GPX3 differences may be associated with alterations in antioxidant capacity and redox regulation, which suggests diverse susceptibility to complex disease and diverse response to relevant drugs in Asians compared with individuals with other ethnic origins.

Original submitted 7 February 2013; Revision submitted 16 May 2013

KEYWORDS::

• ethnicity
• functional prediction analysis
• GPX genes
• haplotype analysis
• selenoproteins

Acknowledgements

The authors are grateful to the research groups of 1000 Genomes Project for their essential contribution.

Financial & competing interests disclosure

This study was supported by PRIN 2009–2011 (prot. n. 200975T9EW) from MIUR. 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

This study was supported by PRIN 2009–2011 (prot. n. 200975T9EW) from MIUR. 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.