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Molecular Genetics and Genomics

, Volume 293, Issue 5, pp 1205–1216 | Cite as

Whole-exome sequencing in maya indigenous families: variant in PPP1R3A is associated with type 2 diabetes

  • Katy Sánchez-Pozos
  • María Guadalupe Ortíz-López
  • Bárbara I. Peña-Espinoza
  • María de los Ángeles Granados-Silvestre
  • Verónica Jiménez-Jacinto
  • Jérôme Verleyen
  • Fasil Tekola-Ayele
  • Alejandro Sanchez-Flores
  • Marta MenjivarEmail author
Original Article

Abstract

It has been presumed that increased susceptibility in Mexicans to type 2 diabetes (T2D) is attributed to the Native American genetic ancestry. Nonetheless, it is not known if there are private genetic variants that confer susceptibility to develop T2D in our population. The Maya indigenous group has the highest proportion of Native American ancestry (98%) which makes it a representative group of the original peoples of Mexico. Thus, the aim of the present study is to identify new genetic variants associated with T2D in Maya families. Whole-exome sequencing was performed on DNA samples from Maya families with a third-generation family history of T2D only in one parental line. Four variants were identified for APOB, PPP1R3A, TPPP2, and GPR1 genes, and were further tested for association with T2D in 600 unrelated Maya in a case–control study. For the first time, rs1799999 in PPP1R3A was associated with risk of T2D in Mayan Mexican individuals (OR = 1.625, P = 0.014). Interestingly, carriers of rs1799999 presented increased values of HOMA-IR. In addition, rs1801702 in APOB was associated with total cholesterol and LDL-C (P = 0.019 and P = 0.020, respectively) in normoglycemic individuals; rs3732083 in GPR1 with HOMA-IR (P = 0.016) and rs9624 in TPPP2 with total cholesterol and triglycerides (P = 0.002 and P = 0.005, respectively) in T2D subjects. Overall, these findings support the idea that there are other genetic variants yet to be described, involved in T2D development in Maya population, being insulin resistance and lipid metabolism the main mechanisms implicated. Thus, these results can contribute to the understanding of diabetes genetic background in Mexican population.

Keywords

Mexican population Type 2 diabetes Maya population Whole-exome sequencing Polymorphism 

Notes

Acknowledgements

SPK was supported by a fellowship of the Program of Postdoctoral Scholarships from DGAPA (UNAM). We would like to thank Ricardo Grande and Gloria Vazquez for the sequencing support as part of the “Unidad de Secuenciación Masiva y Bioinformática” of the “Laboratorio Nacional de Apoyo Tecnológico a las Ciencias Genómicas,” CONACyT #260481, at the Instituto de Biotecnología/UNAM.

Author contributions

SPK performed sample collection, carried out the genotyping, assembled data, statistical analysis, interpreted the results, and wrote the manuscript. OLG and GSMA organized and performed the fieldwork in the indigenous communities for sample collection, and analyzed the biochemical and clinical data, discussed the data, and reviewed manuscript. PEB helped in the sample collection, assembled, and analysis of statistical data. VJ and JJV performed the quality control of sequencing data, the alignment, and the based calling. TAF was involved in data analysis and reviewed the draft of the manuscript. SFA directed the bioinformatic analysis and reviewed the draft of the manuscript. MM conceived, designed, directed the study, analyzed the data, and wrote the manuscript. MM is the guarantor of this work, as such, had full access to all the data in the study, and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors read and approved the final manuscript.

Funding

This investigation was supported by the PAPIIT-DGAPA research Grant IN231511.

Compliance with ethical standards

Conflict of interest

S.P.K. declares that she has no conflict of interest. O.L.G. declares that she has no conflict of interest. G.S.M.A. declares that she has no conflict of interest. P.E.B. declares that she has no conflict of interest. V.J. declares that she has no conflict of interest. J.J.V. declares that he has no conflict of interest. T.A.F. declares that he has no conflict of interest. S.F.A. declares that he has no conflict of interest. M.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.

Data availability

The data that support the findings of this study are available from the authors upon reasonable request and with permission of Dr. Marta Menjivar.

Supplementary material

438_2018_1453_MOESM1_ESM.docx (462 kb)
Supplementary material 1 (DOCX 462 KB)
438_2018_1453_MOESM2_ESM.docx (91 kb)
Supplementary material 2 (DOCX 91 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Katy Sánchez-Pozos
    • 1
    • 3
  • María Guadalupe Ortíz-López
    • 2
  • Bárbara I. Peña-Espinoza
    • 1
  • María de los Ángeles Granados-Silvestre
    • 3
  • Verónica Jiménez-Jacinto
    • 4
  • Jérôme Verleyen
    • 4
  • Fasil Tekola-Ayele
    • 6
  • Alejandro Sanchez-Flores
    • 4
  • Marta Menjivar
    • 1
    • 3
    • 5
    Email author
  1. 1.Laboratorio de Diabetes, Facultad de QuímicaUnidad Académica de Ciencias y Tecnología de la UNAM en Yucatán (PC&TY)MéridaMexico
  2. 2.Laboratorio de Endocrinología MolecularHospital Juárez de MéxicoMexico CityMexico
  3. 3.Facultad de QuímicaUniversidad Nacional Autónoma de MéxicoMexico CityMexico
  4. 4.Unidad Universitaria de Secuenciación Masiva y Bioinformática, Instituto de BiotecnologíaUniversidad Nacional Autónoma de MéxicoCuernavacaMexico
  5. 5.Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de QuímicaUniversidad Nacional Autónoma de México, Instituto Nacional de Medicina GenómicaMexico CityMexico
  6. 6.Epidemiology Branch, Division of Intramural Population Health ResearchEunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of HealthBethesdaUSA

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