Research Progress on High-Altitude Adaptation Characteristics of Bilirubin Metabolism and the Regulatory Role of the UGT1A Gene Family

Abstract

The hypoxic environment at high altitude poses significant challenges to the body’s metabolic system. Bilirubin, as an end product of heme metabolism and an endogenous antioxidant, plays an important role in high-altitude adaptation through its metabolic regulation. This article systematically reviews the characteristic changes in bilirubin metabolism among high-altitude populations and the regulatory mechanisms of the UGT1A gene family. A review of relevant domestic and international research literature indicates that bilirubin levels in high-altitude populations exhibit an altitude-dependent increase, with significant differences between native and migrant populations. Bilirubin participates in high-altitude adaptation through antioxidant and anti-inflammatory mechanisms. UGT1A1 is the key enzyme catalyzing bilirubin glucuronidation, and its gene polymorphisms (UGT1A1*28, *6, etc.) significantly affect enzyme activity and bilirubin levels. The distribution of UGT1A gene frequencies in high-altitude populations is unique and significantly associated with bilirubin phenotypes. Mendelian randomization studies have confirmed a genetic causal relationship between high-altitude adaptation and total bilirubin. Risk prediction models based on UGT1A1 gene polymorphisms have demonstrated application value in the prevention and treatment of neonatal hyperbilirubinemia in plateau regions. In summary, the regulation of bilirubin metabolism mediated by the UGT1A gene family is one of the important mechanisms of high-altitude adaptation in plateau populations. Future multicenter, large-sample functional validation studies are needed to promote its clinical translation in the health management of high-altitude populations.