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Background: Tibetan highlanders have adapted to hypoxic environments through genetic mechanisms that avoid hemoglobin concentration increases and prevent polycythemia. Recently, sex differences in hemoglobin dynamics with age have been reported among Tibetan highlanders living in Tsarang. Additionally, concerns have been raised that dietary changes associated with modernization may increase the risk of polycythemia and lifestyle-related diseases among Tibetan highlanders. However, the relationship between genetic polymorphisms and the risk of lifestyle-related diseases in Tibetan highlanders has been investigated in only a few regions. This study aims to elucidate whether polymorphisms in genes related to hypoxic adaptation are associated with the incidence of lifestyle-related diseases and polycythemia and whether these polymorphisms affect hemoglobin dynamics in the residents of Tsarang, Mustang, Nepal., Methods: Health checkup data from individuals living in Tsarang in Mustang District, Nepal, collected in 2017, were used to determine the prevalence of obesity, hypertension, diabetes, hypoxemia, and polycythemia. DNA was extracted from whole-blood samples, and data for the single-nucleotide polymorphisms (SNPs) rs13419896 (EPAS1), rs12619696 (EPAS1), and rs2790859 (EGLN1) were obtained using real-time PCR. The health checkup data were statistically analyzed to determine the associations of these diseases with polymorphisms in genes related to hypoxic adaptation., Results: A total of 168 participants, comprising 78 males and 90 females, were included in the final analysis. In terms of the prevalence of each disease, only the prevalence of polycythemia significantly differed between sexes (p < 0.01). Additionally, among the three analyzed SNPs, significant sex differences in genotype frequency were observed for rs13419896 and rs2790859. For rs2790859 in females, Tibetan highlanders with the adaptive genotype had a significantly lower incidence of polycythemia (p < 0.01) and significantly lower hemoglobin concentrations (p < 0.01)., Conclusions: This study revealed that there are sex differences in the genotype frequency of gene-related hypoxic adaptations among the residents of Tsarang. The findings also suggested that the rs2790859 polymorphism might be involved in the recent incidence of polycythemia among Tsarang residents. If the frequency of non-Tibetan genotypes increases due to intermixing with other populations in the Mustang District, polycythemia may emerge as a modern disease. It is essential to continue investigating the health status of Mustang residents to elucidate various aspects of hypoxic adaptation and disease susceptibility., (© 2024. The Author(s).)

Background: In Tsarang (at 3560 m), which is located in Mustang, 62.7% of the residents answered that they had a subjective medical history of arthritis, and 41.1% of the residents answered that their families had a subjective medical history of arthritis on a survey conducted in 2017. The expression of hypoxia-inducible factor (HIF) and its effects are deeply involved in hypoxic adaptation in Tibetan highlanders. At the same time, HIF is also related to the onset of rheumatoid arthritis. Therefore, the adaptive mechanism acquired by Tibetan highlanders may promote the development of rheumatoid arthritis. The prevalence of rheumatoid arthritis is estimated to be approximately 0.5-1.0% worldwide. The objective of this study was to estimate the prevalence of rheumatoid arthritis in Tsarang residents using existing diagnostic criteria and to explore its risk factors., Methods: An epidemiological survey was conducted in Tsarang in 2019. Data obtained from anthropometry and questionnaires were statistically analyzed. Biochemical measurements using blood samples were also performed, and the results were used to assess arthritis status. Residents' joint status was scored, and arthritis was assessed based on the clinical disease activity index and ACR/EULAR 2010 criteria., Results: Twenty-seven males and 50 females participated in this survey. In Tsarang, ACR/EULAR 2010 classified 4.3% of males and 7.1% of females as having rheumatoid arthritis, indicating a very high estimated prevalence. We also performed a multivariate analysis to explore its risk factors, and two factors, older age (standardized parameter estimate = 4.84E-01, 95% CI = [9.19E-02, 8.76E-01], p = 0.0170) and a history of living in urban areas (standardized parameter estimate = - 5.49E-01, 95% CI = [- 9.21E-01, 1.77E-01], p = 0.0050), significantly contributed to the higher ACR/EULAR 2010 score in females. In addition, three factors, having no spouse (standardized parameter estimate = 3.17E-01, 95% CI = [5.74E-02, 5.77E-01], p = 0.0179), having a smoking habit (standardized parameter estimate = 2.88E-01, 95% CI = [1.71E-02, 5.59E-01], p = 0.0377), and a history of living in urban areas (standardized parameter estimate = - 3.69E-01, 95% CI = [- 6.83E-01, - 5.60E-02], p = 0.0219), resulted in significantly higher clinical disease activity index scores in females. Furthermore, smoking habits were found to significantly increase blood hyaluronic acid in both males (standardized parameter estimate = 6.03E-01, 95% CI = [3.06E-01, 9.01E-01], p = 0.0020) and females (standardized parameter estimate = 4.87E-01, 95% CI = [5.63E-02, 9.18E-01], p = 0.0291)., Conclusions: In this study, we evaluated the symptoms of arthritis and estimated the prevalence of rheumatoid arthritis using classification criteria for Tibetan highlanders who have adapted to the hypoxic environment and fostered their own culture. The high prevalence of rheumatoid arthritis among Tsarang residents suggests that the hypoxic adaptation mechanism involving HIF in Tibetan highlanders may promote the onset or exacerbation of rheumatoid arthritis. The high prevalence of rheumatoid arthritis among Tibetan highlanders may be related not only to the environmental factors analyzed in this study but also to hypoxic adaptation genes. Further investigation is needed to clarify the genetic factors involved., (© 2022. The Author(s).)