title: Ancestry explains the blunted ventilatory response to sustained hypoxia and lower exercise ventilation of Quechua altitude natives.
abstract: Andean high-altitude (HA) natives have a low (blunted) hypoxic ventilatory response (HVR), lower effective alveolar ventilation, and lower ventilation (VE) at rest and during exercise compared with acclimatized newcomers to HA. Despite blunted chemosensitivity and hypoventilation, Andeans maintain comparable arterial O(2) saturation (Sa(O(2))). This study was designed to evaluate the influence of ancestry on these trait differences. At sea level, we measured the HVR in both acute (HVR-A) and sustained (HVR-S) hypoxia in a sample of 32 male Peruvians of mainly Quechua and Spanish origins who were born and raised at sea level. We also measured resting and exercise VE after 10-12 h of exposure to altitude at 4,338 m. Native American ancestry proportion (NAAP) was assessed for each individual using a panel of 80 ancestry-informative molecular markers (AIMs). NAAP was inversely related to HVR-S after 10 min of isocapnic hypoxia (r = -0.36, P = 0.04) but was not associated with HVR-A. In addition, NAAP was inversely related to exercise VE (r = -0.50, P = 0.005) and ventilatory equivalent (VE/Vo(2), r = -0.51, P = 0.004) measured at 4,338 m. Thus Quechua ancestry may partly explain the well-known blunted HVR (10, 35, 36, 57, 62) at least to sustained hypoxia, and the relative exercise hypoventilation at altitude of Andeans compared with European controls. Lower HVR-S and exercise VE could reflect improved gas exchange and/or attenuated chemoreflex sensitivity with increasing NAAP. On the basis of these ancestry associations and on the fact that developmental effects were completely controlled by study design, we suggest both a genetic basis and an evolutionary origin for these traits in Quechua.
authors.affiliation: Department of Anthropology, 1400 Washington Ave., University at Albany, State University of New York, Albany, NY 12222, USA. tbrutsae@csc.albany.edu
authors.forename: Tom D
authors.initials: TD
authors.lastname: Brutsaert
authors.forename: Esteban J
authors.initials: EJ
authors.lastname: Parra
authors.forename: Mark D
authors.initials: MD
authors.lastname: Shriver
authors.forename: Alfredo
authors.initials: A
authors.lastname: Gamboa
authors.forename: Maria
authors.initials: M
authors.lastname: Rivera-Ch
authors.forename: Fabiola
authors.initials: F
authors.lastname: León-Velarde
mesh_terms: D000328:Adult; D000531:Altitude; D001158:Arteries; D015444:Exercise; D005080:Exercise Test; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D007199:Indians, South American; D008297:Male; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D010568:Peru; D012123:Pulmonary Ventilation; D013030:Spain; D013997:Time Factors; D044465:White People
chemical_list: D010100:Oxygen