MLXIPL is a transcription factor that regulates glycolysis, lipogenesis, and cellular response to hypoxia. A genetic variant of MLXIPL, Gln241His, is highly prevalent in a Tibetan highlander population, and has been thought to be the genetic basis of adaption to high-altitude environments in the Tibetan plateau. In the current study, we tested the association between Gln241His and various physiological parameters in over 3,500 Japanese individuals. Novel strong association was found between Gln241His and increased hemoglobin and hematocrit levels (P = 0.0059 and 0.0019, respectively). Tibetans have adapted to the hypoxia by elevating the ventilation and lowering the hemoglobin concentrations. Therefore, although the Gln241His frequency was higher in Tibetans than in other worldwide populations, it is difficult to consider this variant as a part of the genetic adaptation to hypoxia. The Gln241His-induced changes in glucose and lipid metabolism may explain the high prevalence of Gln241His in Tibetans.
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