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Association of EGLN1 gene with high aerobic capacity of Peruvian Quechua at high altitude.
Brutsaert, Tom D; Kiyamu, Melisa; Elias Revollendo, Gianpietro; Isherwood, Jenna L; Lee, Frank S; Rivera-Ch, Maria; Leon-Velarde, Fabiola; Ghosh, Sudipta; Bigham, Abigail W.
Afiliación
  • Brutsaert TD; Department of Exercise Science, Syracuse University, Syracuse, NY 13244; tdbrutsa@syr.edu.
  • Kiyamu M; Universidad Peruana Cayetano Heredia, Lima, Peru.
  • Elias Revollendo G; Department of Exercise Science, Syracuse University, Syracuse, NY 13244.
  • Isherwood JL; Department of Anthropology, University of Michigan, Ann Arbor, MI 48109-1107.
  • Lee FS; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
  • Rivera-Ch M; Universidad Peruana Cayetano Heredia, Lima, Peru.
  • Leon-Velarde F; Universidad Peruana Cayetano Heredia, Lima, Peru.
  • Ghosh S; Department of Anthropology, North-Eastern Hill University, Shillong, India.
  • Bigham AW; Department of Anthropology, University of Michigan, Ann Arbor, MI 48109-1107.
Proc Natl Acad Sci U S A ; 116(48): 24006-24011, 2019 11 26.
Article en En | MEDLINE | ID: mdl-31712437
Highland native Andeans have resided at altitude for millennia. They display high aerobic capacity (VO2max) at altitude, which may be a reflection of genetic adaptation to hypoxia. Previous genomewide (GW) scans for natural selection have nominated Egl-9 homolog 1 gene (EGLN1) as a candidate gene. The encoded protein, EGLN1/PHD2, is an O2 sensor that controls levels of the Hypoxia Inducible Factor-α (HIF-α), which regulates the cellular response to hypoxia. From GW association and analysis of covariance performed on a total sample of 429 Peruvian Quechua and 94 US lowland referents, we identified 5 EGLN1 SNPs associated with higher VO2max (L⋅min-1 and mL⋅min-1⋅kg-1) in hypoxia (rs1769793, rs2064766, rs2437150, rs2491403, rs479200). For 4 of these SNPs, Quechua had the highest frequency of the advantageous (high VO2max) allele compared with 25 diverse lowland comparison populations from the 1000 Genomes Project. Genotype effects were substantial, with high versus low VO2max genotype categories differing by ∼11% (e.g., for rs1769793 SNP genotype TT = 34.2 mL⋅min-1⋅kg-1 vs. CC = 30.5 mL⋅min-1⋅kg-1). To guard against spurious association, we controlled for population stratification. Findings were replicated for EGLN1 SNP rs1769793 in an independent Andean sample collected in 2002. These findings contextualize previous reports of natural selection at EGLN1 in Andeans, and support the hypothesis that natural selection has increased the frequency of an EGLN1 causal variant that enhances O2 delivery or use during exercise at altitude in Peruvian Quechua.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oxígeno / Polimorfismo de Nucleótido Simple / Altitud / Prolina Dioxigenasas del Factor Inducible por Hipoxia / Hipoxia Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Male País/Región como asunto: America do sul / Peru Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oxígeno / Polimorfismo de Nucleótido Simple / Altitud / Prolina Dioxigenasas del Factor Inducible por Hipoxia / Hipoxia Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Female / Humans / Male País/Región como asunto: America do sul / Peru Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos