Prevalence of hypertension at high altitude: cross-sectional survey in Ladakh, Northern India 2007-2011

Objective: Prevalence of hypertension was examined in a widely dispersed (45 110 km2) representative group of Ladakhi in Northern India. The influence of hypoxic environment of wide-ranged altitude (2600–4900 m) and lifestyle change on hypertension was studied. Methods: 2800 participants (age 20–94 years) were enrolled. Systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure of ≥90 mm Hg and/or taking current anti-hypertensive medicine was defined as hypertension. Height and weight for body mass index and SpO2 were examined. The rural population comprised six subdivisions with a distinct altitude, dietary and occupational pattern. Participants in the urban area of Leh consist of two groups, that is, migrants settled in Leh from the Changthang nomadic area, and dwellers born in Leh. The prevalence of hypertension in the two groups was compared with that in the farmers and nomads in rural areas. The effects of ageing, hypoxia, dwelling at high altitude, obesity, modernised occupation, dwelling in an urban area, and rural-to-urban migration to hypertension were analysed by multiple logistic regression. Results: The prevalence of hypertension was 37.0% in all participants and highest in migrants settled in Leh (48.3%), followed by dwellers born in Leh town (41.1%) compared with those in rural areas (33.5). The prevalence of hypertension in nomads (all: 27.7%, Tibetan/Ladakhi: 19.7/31.9%)) living at higher altitude (4000–4900 m) was relatively low. The associated factors with hypertension were ageing, overweight, dwelling at higher altitude, engagement in modernised sedentary occupations, dwelling in urban areas, and rural-to-urban migration. The effects of lifestyle change and dwelling at high altitude were independently associated with hypertension by multivariate analysis adjusted with confounding factors. Conclusions: Socioeconomic and cultural factors play a big role with the effect of high altitude itself on high prevalence of hypertension in highlanders in Ladakh

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

The Comparison of Comprehensive Geriatric Functions of Community-Dwelling Elderly People Living in Cotahuasi and Puyca Located in La Union Province, Arequipa, Peru

More than 140 million people worldwide live in over 2500 meters highland above sea level. Of them, 80 million live in Asia, and 35 million live in the Andean mountains. This article described the comparison of the comprehensive geriatric functions of community-dwelling elderly people living in Cotahuasi and Puyca located in La Union Province, Arequipa, Peru. The study population consisted of 240 highlanders (mean age: 69.5, male/female: 85/155) living in Cotahuasi (altitude 2, 600-2, 700 m), Pampamarca (3, 000-3, 300 m), Puyca (3, 600 m), and Churca (3, 800 m). All of these towns are located in La Union Province, Arequipa, Peru. Cotahuasi is the capital of La Union Province, and Pampamarca is a rural suburb. Puyca and Churca are rural villages located at higher altitudes (>3, 500 m) along an upper tributary of the Cotahuasi River. The medical survey of community-dwelling elderly people living in these towns was carried out in August in 2010. The scores in ADL, TMIG, FRI, GDS and subjective QOL between Cotahuasi and Puyca were significant differences. The mean age of subjects in Cotahuasi was significantly higher than those in Puyca. The percentage of subjects with diabetes and taking diabetes medicine were significantly higher in Cotahuasi people than in Puyca ones. The percentage of history of stroke and oseoarthropathy were significantly higher in Cotahuasi than in Puyca. We should pay attention to the approximately 10% of the total population in the world were living in mountain areas where socioeconomic globalization was increasing. Further investigations must remit the prevalence of lifestyle-related disease and human ageing phenomena in highlanders

<Award Paper of 4th Congress of Asian Pacific Society of Mountain Medicine (APSMM)>Glucose Intolerance by Interaction between Hypoxia Adaptation and Lifestyle Change in Highlanders in Tibet Plateau

Socioeconomic factors and hypoxia play major roles in the prevalence of glucose intolerance in highlanders. Hypoxemia and polycythemia were closely associated with glucose intolerance after adjustment for the effects of lifestyle changes in our study. Tibetan people may be vulnerable to glucose intolerance, with polycythemia as a sign of poor hypoxic adaptation. Epigenetics is also play a role in its vulnerability with quick lifestyle change. Prevention of lifestyle-related diseases and health education should be advocated, especially in high altitude dwellers with rapidly prevailing socioeconomic globalization

Glucose intolerance associated with hypoxia in people living at high altitudes in the Tibetan highland

Objectives: To clarify the association between glucose intolerance and high altitudes (2900-4800 m) in a hypoxic environment in Tibetan highlanders and to verify the hypothesis that high altitude dwelling increases vulnerability to diabetes mellitus (DM) accelerated by lifestyle change or ageing. Design: Cross-sectional epidemiological study on Tibetan highlanders. Participants: We enrolled 1258 participants aged 40-87 years. The rural population comprised farmers in Domkhar (altitude 2900-3800 m) and nomads in Haiyan (3000-3100 m), Ryuho (4400 m) and Changthang (4300-4800 m). Urban area participants were from Leh (3300 m) and Jiegu (3700 m). Main outcome measure: Participants were classified into six glucose tolerance-based groups: DM, intermediate hyperglycaemia (IHG), normoglycaemia (NG), fasting DM, fasting IHG and fasting NG. Prevalence of glucose intolerance was compared in farmers, nomads and urban dwellers. Effects of dwelling at high altitude or hypoxia on glucose intolerance were analysed with the confounding factors of age, sex, obesity, lipids, haemoglobin, hypertension and lifestyle, using multiple logistic regression. Results: The prevalence of DM (fasting DM)/IHG (fasting IHG) was 8.9% (6.5%)/25.1% (12.7%), respectively, in all participants. This prevalence was higher in urban dwellers (9.5% (7.1%)/28.5% (11.7%)) and in farmers (8.5% (6.1%)/28.5% (18.3%)) compared with nomads (8.2% (5.7%)/15.7% (9.7%)) (p=0.0140/0.0001). Dwelling at high altitude was significantly associated with fasting IHG+fasting DM/fasting DM (ORs for >4500 and 3500-4499 m were 3.59/4.36 and 2.07/1.76 vs <3500 m, respectively). After adjusting for lifestyle change, hypoxaemia and polycythaemia were closely associated with glucose intolerance. Conclusions: Socioeconomic factors, hypoxaemia and the effects of altitudes ≥3500 m play a major role in the high prevalence of glucose intolerance in highlanders. Tibetan highlanders may be vulnerable to glucose intolerance, with polycythaemia as a sign of poor hypoxic adaptation, accelerated by lifestyle change and ageing

Challenges of Field Medicine from Japan to The “Himalaya Model of Lifestyle-Related Diseases” (特集2: フィールド医学)

特集2: フィールド医学 = Special Issue 2: Field Medicine本誌公刊にあたっては、京都大学学士山岳会、京都大学「霊長類学・ワイルドライフサイエンス」・リーディング大学院からの助成をうけました