Advertisement

Molecular Biology Reports

, Volume 45, Issue 6, pp 2525–2533 | Cite as

Genetic variability among Mexican Mestizo and Amerindian populations based on three ABCB1 polymorphisms

  • Alma Faviola Favela-Mendoza
  • Héctor Rangel-Villalobos
  • Ingrid Fricke-Galindo
  • Alberto Ortega-Vázquez
  • Gabriela Martínez-Cortés
  • Marisol López-López
Original Article
  • 75 Downloads

Abstract

The most widely studied polymorphisms of the ABCB1 gene are rs1128503 (c.1236C>T), rs2032582 (c.2677G>T/A), and rs1045642 (c.3435C>T). Although variation in ABCB1 allele frequencies among Mexican Mestizos (admixed) from different regions has been observed, Mexican Amerindians have been poorly studied. We aimed to describe the genetic variability of these three ABCB1 polymorphisms in a total sample of 273 Mexican volunteers that included Mestizos from the state of Yucatán, and Amerindians from seven populations (Tarahumara, Mayo, Huichol, Purépecha, Nahua, Tojolabal, and Maya). Genotypes were determined by means of Taq Man probes (qPCR). Genotype distribution was in Hardy–Weinberg equilibrium for all three ABCB1polymorphisms in the eight Mexican populations analyzed. For c.1236C>T and c.3435C>T, the heterozygous C/T was the most frequent genotype in the majority of the studied Mexican populations (range 30.8–65.4%), while heterozygous G/T was the most common genotype for c.2677G>T/A (range 25.9–51.2%), mainly followed by G/G (range 3.2–47.1%) and T/T (range 7.0–35.5%). 12 haplotypes were estimated from the three ABCB1 polymorphisms analyzed, with TTT the most frequent haplotype (mean, 37.0%). Genetic differentiation was demonstrated among the studied Mexican populations (Fst p value < 0.0001), which could imply a diverse drug response or a risk for adverse drug reactions to ABCB1 substrates. Although differences among Amerindians are probably due to genetic drift effects, for Mestizos this could imply variation in admixture composition. In conclusion, interpopulation variability in the observed frequencies of ABCB1 polymorphisms among Mexican Mestizos and Amerindians allow predicting diverse drug responses to ABCB1 substrates in these populations.

Keywords

ABCB1 Polymorphism Mexican population Mestizos Amerindians Pharmacogenetics 

Notes

Acknowledgements

The authors are grateful for the generous participation of indigenous volunteers in this study. We also thank CONACYT-México (Grant #167261) for financial support.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflicts of interest.

Supplementary material

11033_2018_4419_MOESM1_ESM.tiff (6.6 mb)
Online Resource 1: Geographic distribution of the Mexican population samples studied herein for three ABCB1 variants. (TIFF 6803 KB)
11033_2018_4419_MOESM2_ESM.docx (50 kb)
Supplementary material 2 (DOCX 49 KB)

References

  1. 1.
    Hodges LM, Markova SM, Chinn LW, Gow JM, Kroetz DL, Klein TE, Altman RB (2011) Very important pharmacogene summary: ABCB1 (MDR1, P-glycoprotein). Pharmacogenet Genomics 21(3):152–161CrossRefGoogle Scholar
  2. 2.
    Chen Z, Shi T, Zhang L et al (2016) Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: a review of the past decade. Cancer Lett 370(1):153–164CrossRefGoogle Scholar
  3. 3.
    Chen Z, Zhang L, Yang C, Jiang Z, Shen H, Gui G (2017) Effect of MDR1 C1236T polymorphism on cyclosporine pharmacokinetics. A systematic review and meta-analysis. Medicine (Baltimore) 96(47):e8700.  https://doi.org/10.1097/MD.0000000000008700 CrossRefGoogle Scholar
  4. 4.
    Kim RB (2002) Drugs as P-glycoprotein substrates, inhibitors, and inducers. Drug Metab 34:47–54CrossRefGoogle Scholar
  5. 5.
    León-Cachón RBR, Ascacio-Martínez JA, Gamino-Peña ME et al (2016) A pharmacogenetic pilot study reveals MTHFR. DRD3, and MDR1 polymorphisms as biomarker candidates for slow atorvastatin metabolizers. BMC Cancer 16:74.  https://doi.org/10.1186/s12885-016-2062-2 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Dutheil F, Jacob A, Dauchy S, Beaune P, Scherrmann JM, Declèves X, Loriot MA (2010) ABC transporters and cytochromes P450 in the human central nervous system: influence on brain pharmacokinetics and contribution to neurodegenerative disorders. Expert Opin Drug Metab Toxicol 6(10):1161–1174.  https://doi.org/10.1517/17425255.2010.510832 CrossRefPubMedGoogle Scholar
  7. 7.
    Elali A, Rivest S (2013) The role of ABCB1 and ABCA1 in beta-amyloid clearance at the neurovascular unit in Alzheimer’s disease. Front Physiol 4:45CrossRefGoogle Scholar
  8. 8.
    Calderón-Cruz B, Rodríguez-Galván K, Manzo-Francisco LA et al (2015) C3435T polymorphism of the ABCB1 gene is associated with poor clopidogrel responsiveness in a Mexican population undergoing percutaneous coronary intervention. Thromb Res 136(5):894–898.  https://doi.org/10.1016/j.thromres.2015.08.025 CrossRefPubMedGoogle Scholar
  9. 9.
    Zhang YT, Yang LP, Shao H, Li KX, Sun CH, Shi LW (2008) ABCB1 polymorphisms may have a minor effect on cyclosporine blood concentrations in myasthenia gravis patients. Brit J Clin Pharmacol 66:240–246CrossRefGoogle Scholar
  10. 10.
    Tovilla-Zárate CA, Vargas I, Hernández S et al (2014) Association study between the MDR1 gene and clinical characteristics in schizophrenia. Rev Bras Psiquiatr 36(3):227–232.  https://doi.org/10.1590/1516-4446-2013-1270 CrossRefPubMedGoogle Scholar
  11. 11.
    Ortega-Vázquez A, Dorado P, Fricke-Galindo I et al (2016) CYP2C19, ABCB1 genetic polymorphisms and phenytoin plasma concentrations in Mexican-Mestizo patients with epilepsy. Pharmacogenomics J 9(3):286–292.  https://doi.org/10.1038/tpj.2015.45 CrossRefGoogle Scholar
  12. 12.
    Kim RB, Leake BF, Choo EF et al (2001) Identification of functionally variant MDR1 alleles among European Americans and African Americans. Clin Pharmacol Ther 70(2):189–199CrossRefGoogle Scholar
  13. 13.
    Rubi-Castellanos R, Martínez-Cortés G, Muñoz-Valle JF, González-Martín A, Cerda-Flores RM, Anaya-Palafox M, Rangel-Villalobos H (2009) Pre-Hispanic mesoamerican demography approximates the present-day ancestry of Mestizos throughout the territory of Mexico. Am J Phys Anthropol 139(3):284–294.  https://doi.org/10.1002/ajpa.20980 CrossRefPubMedGoogle Scholar
  14. 14.
    Rangel-Villalobos H, Martínez-Sevilla VM, Martínez-Cortés G, Aguilar-Velázquez JA, Sosa-Macías M, Rubi-Castellanos R, González-Martín A (2016) Importance of the geographic barriers to promote gene drift and avoid pre- and post-Columbian gene flow in Mexican native groups: evidence from forensic STR Loci. Am J Phys Anthropol 160(2):298–316.  https://doi.org/10.1002/ajpa.22969 CrossRefPubMedGoogle Scholar
  15. 15.
    Fricke-Galindo I, Jung-Cook H, LLerena A, López-López M (2016) Interethnic variability of pharmacogenetic biomarkers in Mexican healthy volunteers: a report from the RIBEF (Ibero-American Network of Pharmacogenetics and Pharmacogenomics). Drug Metab Pers Ther 31(2):61–81.  https://doi.org/10.1515/dmpt-2015-0030.Review CrossRefPubMedGoogle Scholar
  16. 16.
    Vargas-Alarcón G, Ramírez-Bello J, de la Peña A et al (2014) Distribution of ABCB1, CYP3A5, CYP2C19, and P2RY12 gene polymorphisms in a Mexican Mestizos population. Mol Biol Rep 19(10):7023–7029.CrossRefGoogle Scholar
  17. 17.
    Gutiérrez-Rubio SA, Quintero-Ramos A, Durán-Cárdenas A et al (2015) 1236 C/T and 3435 C/T polymorphisms of the ABCB1 gene in Mexican breast cancer patients. Genet Mol Res 14(1):1250–1259.  https://doi.org/10.4238/2015 CrossRefPubMedGoogle Scholar
  18. 18.
    Escalante-Santiago D, Feria-Romero IA, Ribas-Aparicio RM et al (2014) MDR-1 and MRP2 gene polymorphisms in Mexican epileptic pediatric patients with complex partial seizures. Front Neurol 5:184.  https://doi.org/10.3389/fneur.2014.00184 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Rodríguez-Castillo JA, Arce-Mendoza AY, Quintanilla-Siller A, Rendon A, Salinas-Carmona MC, Rosas-Taraco AG (2015) Possible association of rare polymorphism in the ABCB1 gene with rifampin and ethambutol drug-resistant tuberculosis. Tuberculosis (Edinb) 95(5):532–537.  https://doi.org/10.1016/j.tube.2015.04.004 CrossRefGoogle Scholar
  20. 20.
    Marsh S, King CR, Van Booven DJ, Revollo JY, Gilman RH, McLeod HL (2015) Pharmacogenomic assessment of Mexican and Peruvian populations. Pharmacogenomics 16(5):441–448CrossRefGoogle Scholar
  21. 21.
    Zaruma-Torres F, Lares-Asseff I, Lima A et al (2016) Genetic polymorphisms associated to folate transport as predictors of increased risk for acute lymphoblastic leukemia in Mexican children. Front Pharmacol 7:238.  https://doi.org/10.3389/fphar.2016.00238 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Jin SS, Song WJ (2017) Association between MDR1 C3435T polymorphism and colorectal cancer risk: a meta-analysis. Medicine (Baltimore) 96(51):e9428.  https://doi.org/10.1097/MD.0000000000009428 CrossRefGoogle Scholar
  23. 23.
    Acuña-Alonzo V, Flores-Dorantes T, Kruit JK et al (2010) A functional ABCA1 gene variant is associated with low HDL-cholesterol levels and shows evidence of positive selection in Native Americans. Hum Mol Genet 19:2877–2885CrossRefGoogle Scholar
  24. 24.
    Williams AL, Jacobs SB, Moreno-Macías H et al (2014) Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico. Nature 506:97–101CrossRefGoogle Scholar
  25. 25.
    Peakall R, Smouse PE (2012) GenAlEx 6.5: genetic analysis in Excel. Population genetic software for teaching and research-an update. Bioinformatics 28(19):2537–2539CrossRefGoogle Scholar
  26. 26.
    Excoffier L, Laval G, Schneider S (2005) Arlequin ver. 3.0: An integrated software package for population genetics data analysis. Evol Bioinform Online 1:47–50CrossRefGoogle Scholar
  27. 27.
    Yoo J, Lee Y, Kim Y, Rha SY, Kim Y (2008) SNPAnalyzer 2.0: a web-based integrated workbench for linkage disequilibrium analysis and association analysis. BMC Bioinform 9:290.  https://doi.org/10.1186/1471-2105-9-290 CrossRefGoogle Scholar
  28. 28.
    Macías-Gómez NM, Gutiérrez-Angulo M, Leal-Ugarte E et al (2014) MDR1 C3435T polymorphism in Mexican patients with breast cancer. Genet Mol Res 13(3):5018–5024.  https://doi.org/10.4238/2014.July.4.17 CrossRefPubMedGoogle Scholar
  29. 29.
    Leal-Ugarte E, Gutiérrez-Angulo M, Macías-Gómez NM et al (2008) MDR1 C3435T polymorphism in Mexican children with acute lymphoblastic leukemia and in healthy individuals. Hum Biol 80(4):449–455.  https://doi.org/10.3378/1534-6617-80.4.449 CrossRefPubMedGoogle Scholar
  30. 30.
    Santos PC, Soares RA, Santos DB et al (2011) CYP2C19 and ABCB1 gene polymorphisms are differently distributed according to ethnicity in the Brazilian general population. BMC Medical Genetics 12:13.  https://doi.org/10.1186/1471-2350-12-13 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Dudarewicz M, Barańska M, Rychlik-Sych M et al (2012) C3435T polymorphism of the ABCB1/MDR1 gene encoding P-glycoprotein in patients with inflammatory bowel disease in a Polish population. Pharmacol Rep 64(2):343–350CrossRefGoogle Scholar
  32. 32.
    Balram C, Sharma A, Sivathasan C et al (2003) Frequency of C3435T single nucleotide MDR1 genetic polymorphism in an Asian population: phenotypic–genotypic correlates. Br J Clin Pharmacol 56(1):78–83.  https://doi.org/10.1046/j.1365-2125.2003.01820.x CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Ameyaw MM, Regateiro F, Li T et al (2001) MDR1 pharmacogenetics: frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity. Pharmacogenetics 11(3):217–221CrossRefGoogle Scholar
  34. 34.
    Silva-Zolezzi I, Hidalgo-Miranda A, Estrada-Gil J (2009) Analysis of genomic diversity in Mexican Mestizo populations to develop genomic medicine in Mexico. Proc Natl Acad Sci USA 106(21):8611–8616.  https://doi.org/10.1073/pnas.0903045106 CrossRefPubMedGoogle Scholar
  35. 35.
    Moreno-Estrada A, Gignoux CR, Fernández-López JC et al (2014) The genetics of Mexico recapitulates Native American substructure and affects biomedical traits. Science 344:1280–1285. ( https://doi.org/10.1126/science.1251688) CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  • Alma Faviola Favela-Mendoza
    • 1
  • Héctor Rangel-Villalobos
    • 1
  • Ingrid Fricke-Galindo
    • 2
  • Alberto Ortega-Vázquez
    • 2
  • Gabriela Martínez-Cortés
    • 1
  • Marisol López-López
    • 2
  1. 1.Instituto de Investigación en Genética Molecular, Centro Universitario de la CiénegaUniversidad de Guadalajara (CUCiénega-UdeG)OcotlánMexico
  2. 2.Departamento de Sistemas BiológicosUniversidad Autónoma Metropolitana (UAM) Unidad XochimilcoMexico CityMexico

Personalised recommendations