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Ventilatory Chemoreflexes and HMOX2 Variation in Individuals of Himalayan and Han Chinese Ancestry Residing at Sea Level
Author(s) -
Heinrich Erica C,
Djokic Matea,
Powell Frank L,
Simonson Tatum S
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb840
Subject(s) - han chinese , altitude (triangle) , biology , physiology , effects of high altitude on humans , sea level , demography , genetics , gene , geography , single nucleotide polymorphism , genotype , physical geography , geometry , mathematics , anatomy , sociology
Humans have lived on the Tibetan Plateau (>4,000 m) for thousands of years and exhibit distinct patterns of adaptation to high altitude. Individuals with Tibetan ancestry living at high altitude for their entire life have a greater hypoxic ventilatory response (HVR) than Han Chinese and Andeans resident at comparable altitudes. Tibetan highlanders also exhibit lower average hemoglobin concentration, a trait associated with SNP variants in the heme oxygenase 2 gene ( HMOX2 ). The genomic region containing HMOX2 displays a strong signal of selection in several independent studies in Tibetans and HMOX2 has been linked to hypoxic chemosensitivity via carbon monoxide‐sensitive hydrogen sulfide signaling in the carotid body. The goals of our study were (1) to determine if HVR remains elevated in ancestral Tibetans residing at sea level and (2) to determine if putatively adaptive HMOX2 variants are associated with HVR in populations at sea level. We measured isocapnic HVR, hypercapnic ventilatory response (HCVR), and hematocrits in individuals of Himalayan ancestry (HA, Tibetan or Nepalese, female = 4; male = 3) or Han Chinese (HC, male = 7; female = 17) ancestry residing at sea level. We found no difference in the HVR across HA and HC men or women at sea level (men: HA=0.17±0.25, HC: 0.14±0.13 L min −1 %SaO2 −1 , NS; women: HA: 0.13±0.08, HC: 0.27±0.22, NS). However, HA women show decreased HCVR (HA: 0.14±0.14, HC: 0.59±0.28 L min −1 torr −1 , p <0.01) and HA men show increased resting ventilation (HA: 10.85±1.86, HC: 7.58±1.66 L min −1 , p <0.02) compared to HC women and men, respectively. Both HA men and women exhibit a higher resting oxygen saturation compared to HC (HA: 99.02±1.02, HC: 97.93±1.07%, p <0.02). Similar to previous observations, hematocrits tend to be lower on average in both HA men (HA: 43.1 ± 1.99; HC: 45.6 ± 2.34, p <0.14) and women (HA: 37.4±3.9; HC: 40.2±2.4, p <0.07). Our data show that the HVR in sea level residents of HA and HC ancestry are not different, suggesting that increases in the HVR with ventilatory acclimatization or decreases hypoxic desensitization (i.e. “blunting”) differs between these populations. We are completing SNP genotyping of HMOX2 in these populations based on Tibetan‐specific adaptive signals to determine if the HVR is associated with those adaptive variants. Support or Funding Information This work was supported by an NIH Ruth L. Kirschstein National Research Service Award (NRSA).