Abstract
Kinota, Fumiya, Yunden Droma, Nobumitsu Kobayashi, Toshimichi Horiuchi, Yoshiaki Kitaguchi, Masanori Yasuo, Masao Ota, and Masayuki Hanaoka. The contribution of genetic variants of the gene encoding peroxisome proliferator-activated receptor-alpha gene (PPARA) to high-altitude hypoxia adaptation in Sherpa highlanders. High Alt Med Biol. 24:186-192, 2023.-Sherpa highlanders, who play invaluable roles in the exploration of Mount Everest, have exceptional tolerance to hypobaric hypoxia. Sherpa people are well known to possess the traits determined by genetic background for high-altitude adaptation. The metabolic adaptation mechanism is one of the biological ways for Sherpa highlanders in protecting them from hypoxia stress at high altitude. Studies have suggested that the gene encoding PPARA is associated with metabolic adaptation in the Himalayan population of Tibetans. This study attempts to investigate the genetic variants of the PPARA in Sherpa highlanders and the association with high-altitude hypoxia adaptation. Seven single-nucleotide polymorphisms (SNPs; rs135547, rs5769178, rs881740, rs4253712, rs5766741, and rs5767700 in introns and rs1800234 in exon 6) in the PPARA were genotyped in 105 Sherpa highlanders who lived in the Khumbu region (3440 m above sea level) and 111 non-Sherpa lowlanders who resided in Kathmandu (1300 m) in Nepal. By means of analyses of genetic distances, genotype distributions, allele frequencies, linkage disequilibrium, and haplotype constructions of the seven SNPs in the Sherpa highlanders versus the non-Sherpa lowlanders, it was revealed that the frequencies of minor alleles of rs4253712, rs5766741, rs5767700, and rs1800234 SNPs, as well as the frequency of haplotype constructed by the minor alleles of rs5766741-rs5767700-rs1800234, were significantly overrepresented in the Sherpa highlanders in comparison with the non-Sherpa lowlanders. The results strongly suggest that the genetic variants of the PPARA are likely to contribute to the high-altitude adaptation in Sherpa highlanders.
Highlights
Sherpa highlanders, who play invaluable roles in the exploration of Mount Everest, have exceptional tolerance to hypobaric hypoxia
Seven single-nucleotide polymorphisms (SNPs; rs135547, rs5769178, rs881740, rs4253712, rs5766741, and rs5767700 in introns and rs1800234 in exon 6) in the peroxisome proliferator-activated receptor-alpha gene (PPARA) were genotyped in 105 Sherpa highlanders who lived in the Khumbu region (3440 m above sea level) and 111 non-Sherpa lowlanders who resided in Kathmandu (1300 m) in Nepal
The genotype distributions and allele frequencies for each of the seven SNPs in the PPARA were in Hardy–Weinberg equilibrium (HWE) for the two study groups
Summary
Sherpa highlanders, who play invaluable roles in the exploration of Mount Everest, have exceptional tolerance to hypobaric hypoxia. Sherpa people are well known to possess the traits for high-altitude adaptation (Hochachka et al, 1996a, 1996b; Horscroft et al, 2017). Physiological systems such as the respiratory system,. Cardiac vasculature, and hematology are adaptive to highaltitude hypoxia, with Sherpas showing phenotypes of increased lung diffusing capacity, elevated levels of bioactive nitric oxide products and other biovasodilators, and unelevated hemoglobin levels that sustain physiological functions at sea level rates under conditions of hypobaric hypoxia (Hanaoka et al, 2012; Gilbert-Kawai et al, 2014). The heart and brain are two organs of the human body that has the highest oxygen demands and the lowest rates of ATP production and utilization (Stanley et al, 2005; Du et al, 2008)
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