title: Genetic variation in hypoxia-inducible factor 1alpha and its possible association with high altitude adaptation in Sherpas.
abstract: Hypoxic stress at high altitude requires adaptations in several physiological functions to ensure the optimal oxygenation of all cells. Several lines of evidence suggested that high-altitude native populations such as Sherpas have been genetically adapted to their stressful environment. We investigated the genetic variation in the hypoxia-inducible factor (HIF)-1alpha gene in Sherpas as compared with Japanese, native lowlanders, and found a novel dinucleotide repeat polymorphism in intron 13 of the HIF-1alpha gene. GT15 allele was more frequent in Japanese than in Sherpas with statistical significance, while GT14 allele was significantly more frequent in Sherpas as compared with Japanese. A possible genetic variation in the HIF-1alpha gene might function in adaptation to living at high altitude. Because the activity of HIF-1 is regulated by multiple steps including the transcriptional level, the effect of the polymorphism in intron 13 on the cellular hypoxic responses remains to be elucidated.
authors.affiliation: Department of Molecular Predictive Medicine and Sport Science, Kyorin University, School of Medicine, Mitaka, Tokyo, Japan. kenjiszk@se.ritsumei.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: T
authors.initials: T
authors.lastname: Kizaki
authors.forename: Y
authors.initials: Y
authors.lastname: Hitomi
authors.forename: M
authors.initials: M
authors.lastname: Nukita
authors.forename: K
authors.initials: K
authors.lastname: Kimoto
authors.forename: N
authors.initials: N
authors.lastname: Miyazawa
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Ohnuki
authors.forename: H
authors.initials: H
authors.lastname: Ohno
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000483:Alleles; D000531:Altitude; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002883:Chromosomes, Human, Pair 14; D004268:DNA-Binding Proteins / Q000235:genetics*; D018900:Dinucleotide Repeats; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007438:Introns; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors