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Susceptibility background for type 2 diabetes in eleven Mexican Indigenous populations: HNF4A gene analysis

Abstract

The genetic risk of developing type 2 diabetes (T2D) increases in parallel with the proportion of Native American ancestry. Mestizo Mexicans have a 70% Native Amerindian genetic background. The T130I polymorphism in the HNF4A gene has been associated with early-onset T2D in mestizo Mexicans. Thus, the aim of the present study was to evaluate the frequency and relationship of the T130I variant in the HNF4A gene with risk factors for developing T2D in eleven indigenous groups from Mexico. In two groups, all exons of the HNF4A gene were directly sequenced; in the remaining the T130I polymorphism was analyzed by restriction fragment length polymorphism. Ancestry informative markers were assessed to confirm the Amerindian component. An additional analysis of EHH was carried out. Interestingly, HNF4A gene screening revealed only the presence of the T130I polymorphism. The range frequency of the risk allele (T) in the indigenous groups was from 2.7 to 16%. Genotypic frequencies (T130I/I130I) were higher and significantly different from those of all of the populations included in the HapMap Project (P < 0.005). EHH scores suggest a positive selection for T130I polymorphism. Metabolic traits indicate a relationship between the T130I/I130I genotypes with high triglyceride concentrations in the indigenous groups (P < 0.005). These results strongly suggest that the high frequency of the T130I polymorphism and its biological relationship with dysfunction in lipid metabolism in Mexican indigenous groups is a risk factor for the developing of T2D in Mexicans.

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Acknowledgements

We thank the Health Departments of each of the participating States.

Author information

Correspondence to M. Menjivar.

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Funding

This study was funded by CONACYT (scholarship 201106) and PAPIIT-DGAPA (Grant no. IN208507).

Conflict of interest

Granados-Silvestre MA declares that she has no conflict of interest; Ortiz-López MG declares that she has no conflict of interest; Granados J declares that he has no conflict of interest; Canizales-Quinteros S declares that he has no conflict of interest; Rosenda I Peñaloza-Espinosa declares that she has no conflict of interest; Lechuga C declares that she has no conflict of interest; Acuña-Alonzo V declares that he has no conflict of interest; Sánchez-Pozos K declares that she has no conflict of interest and Menjívar M declares that she has no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent: Informed consent was obtained from all individual participants included in the study.

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Communicated by S. Hohmann.

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Granados-Silvestre, M.A., Ortiz-López, M.G., Granados, J. et al. Susceptibility background for type 2 diabetes in eleven Mexican Indigenous populations: HNF4A gene analysis. Mol Genet Genomics 292, 1209–1219 (2017). https://doi.org/10.1007/s00438-017-1340-2

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Keywords

  • Mexican indigenous
  • T130I polymorphism
  • Diabetes background
  • HNF4A gene