{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T15:34:38Z","timestamp":1769268878963,"version":"3.49.0"},"reference-count":48,"publisher":"Portland Press Ltd.","issue":"6","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,3,1]]},"abstract":"<jats:p>HAPE (high-altitude pulmonary oedema) is characterized by pulmonary hypertension, vasoconstriction and an imbalance in oxygen-sensing redox switches. Excess ROS (reactive oxygen species) contribute to endothelial damage under hypobaric hypoxia, hence the oxidative-stress-related genes CYBA (cytochrome b\u2212245 \u03b1 polypeptide) and GSTP1 (glutathione transferase Pi 1) are potential candidate genes for HAPE. In the present study, we investigated the polymorphisms \u2212930A\/G and H72Y (C\/T) of CYBA and I105V (A\/G) and A114V (C\/T) of GSTP1, individually and in combination, in 150 HAPE-p (HAPE patients), 180 HAPE-r (HAPE-resistant lowland natives) and 180 HLs (healthy highland natives). 8-Iso-PGF2\u03b1 (8-iso-prostaglandin F2\u03b1) levels were determined in plasma and were correlated with individual alleles, genotype, haplotype and gene\u2013gene interactions. The relative expression of CYBA and GSTP1 were determined in peripheral blood leucocytes. The genotype distribution of \u2212930A\/G, H72Y (C\/T) and I105V (A\/G) differed significantly in HAPE-p compared with HAPE-r and HLs (P\u22640.01). The haplotypes G-C of \u2212930A\/G and H72Y (C\/T) in CYBA and G-C and G-T of I105V (A\/G) and A114V (C\/T) in GSTP1 were over-represented in HAPE-p; in contrast, haplotypes A-T of \u2212930A\/G and H72Y (C\/T) in CYBA and A-C of I105V (A\/G) and A114V (C\/T) in GSTP1 were over-represented in HAPE-r and HLs. 8-Iso-PGF2\u03b1 levels were significantly higher in HAPE-p and in HLs than in HAPE-r (P=2.2\u00d710\u221216 and 1.2\u00d710\u221214 respectively) and the expression of CYBA and GSTP1 varied differentially (P&amp;lt;0.05). Regression analysis showed that the risk alleles G, C, G and T of \u2212930A\/G, H72Y (C\/T), I105V (A\/G) and A114V (C\/T) were associated with increased 8-iso-PGF2\u03b1 levels (P&amp;lt;0.05). Interaction between the two genes revealed over-representation of most of the risk-allele-associated genotype combinations in HAPE-p and protective-allele-associated genotype combinations in HLs. In conclusion, the risk alleles of CYBA and GSTP1, their haplotypes and gene\u2013gene interactions are associated with imbalanced oxidative stress and, thereby, with high-altitude adaptation and mal-adaptation.<\/jats:p>","DOI":"10.1042\/cs20110205","type":"journal-article","created":{"date-parts":[[2011,10,7]],"date-time":"2011-10-07T21:26:14Z","timestamp":1318022774000},"page":"299-311","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["<i>CYBA<\/i>and<i>GSTP1<\/i>variants associate with oxidative stress under hypobaric hypoxia as observed in high-altitude pulmonary oedema"],"prefix":"10.1042","volume":"122","author":[{"given":"Aastha","family":"Mishra","sequence":"first","affiliation":[{"name":"Institute of Genomics and Integrative Biology, Delhi, India"},{"name":"Department of Biotechnology, University of Pune, Pune, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zahara","family":"Ali","sequence":"additional","affiliation":[{"name":"Institute of Genomics and Integrative Biology, Delhi, India"},{"name":"Department of Biotechnology, University of Pune, Pune, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arpana","family":"Vibhuti","sequence":"additional","affiliation":[{"name":"Institute of Genomics and Integrative Biology, Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rahul","family":"Kumar","sequence":"additional","affiliation":[{"name":"Institute of Genomics and Integrative Biology, Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Perwez","family":"Alam","sequence":"additional","affiliation":[{"name":"Institute of Genomics and Integrative Biology, Delhi, India"},{"name":"Department of Biotechnology, University of Pune, Pune, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rekhbala","family":"Ram","sequence":"additional","affiliation":[{"name":"Institute of Genomics and Integrative Biology, Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tashi","family":"Thinlas","sequence":"additional","affiliation":[{"name":"Department of Medicine, Sonam Norboo Memorial Hospital, Leh, Ladakh, Jamu & Kashmir, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghulam","family":"Mohammad","sequence":"additional","affiliation":[{"name":"Department of Medicine, Sonam Norboo Memorial Hospital, Leh, Ladakh, Jamu & Kashmir, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. A. Qadar","family":"Pasha","sequence":"additional","affiliation":[{"name":"Institute of Genomics and Integrative Biology, Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2011,11,22]]},"reference":[{"key":"2021113010204426600_B1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1089\/152702904322963690","article-title":"Increased oxidative stress following acute and chronic high altitude exposure","volume":"5","author":"Jefferson","year":"2004","journal-title":"High Alt. Med. Biol."},{"key":"2021113010204426600_B2","doi-asserted-by":"crossref","first-page":"4837","DOI":"10.1113\/jphysiol.2010.194704","article-title":"High-altitude pulmonary hypertension is associated with a free radical-mediated reduction in pulmonary nitric oxide bioavailability","volume":"588","author":"Bailey","year":"2010","journal-title":"J. Physiol."},{"key":"2021113010204426600_B3","first-page":"513","article-title":"A potential role for free radicalmediated skeletal muscle soreness in the pathophysiology of acute mountain sickness","volume":"72","author":"Bailey","year":"2001","journal-title":"Aviat. Space Environ. Med."},{"key":"2021113010204426600_B4","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1152\/japplphysiol.01167.2004","article-title":"Physiological aspects of high-altitude pulmonary edema","volume":"98","author":"Bartsch","year":"2005","journal-title":"J. Appl. Physiol."},{"key":"2021113010204426600_B5","doi-asserted-by":"crossref","first-page":"789","DOI":"10.7326\/0003-4819-141-10-200411160-00010","article-title":"The physiologic basis of high-altitude diseases","volume":"141","author":"West","year":"2004","journal-title":"Ann. Intern. Med."},{"key":"2021113010204426600_B6","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1093\/jn\/129.11.2009","article-title":"Oxidative stress in humans during work at moderate altitude","volume":"129","author":"Chao","year":"1999","journal-title":"J. Nutr."},{"key":"2021113010204426600_B7","doi-asserted-by":"crossref","first-page":"23317","DOI":"10.1074\/jbc.271.38.23317","article-title":"p22phox is a critical component of the superoxide-generating NADH\/NADPH oxidase system and regulates angiotensin II-induced hypertrophy in vascular smooth muscle cells","volume":"271","author":"Ushio-Fukai","year":"1996","journal-title":"J. Biol. Chem."},{"key":"2021113010204426600_B8","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1161\/01.RES.0000063424.28903.BB","article-title":"Increased superoxide generation is associated with pulmonary hypertension in fetal lambs: a role for NADPH oxidase","volume":"92","author":"Brennan","year":"2003","journal-title":"Circ. Res."},{"key":"2021113010204426600_B9","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1161\/01.HYP.0000134790.02026.e4","article-title":"Functional effect of the p22phox \u2212930A\/G polymorphism on p22phox expression and NADPH oxidase activity in hypertension","volume":"44","author":"San Jos\u00e9","year":"2004","journal-title":"Hypertension"},{"key":"2021113010204426600_B10","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1097\/01.hjh.0000234110.54110.56","article-title":"The C242T CYBA polymorphism of NADPH oxidase is associated with essential hypertension","volume":"24","author":"Moreno","year":"2006","journal-title":"J. Hypertens."},{"key":"2021113010204426600_B11","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1160\/TH10-08-0529","article-title":"The effect of p22-PHOX (CYBA) polymorphisms on premature coronary artery disease (\u2264 40\u00a0years of age)","volume":"105","author":"Goliasch","year":"2011","journal-title":"Thromb. Haemostasis"},{"key":"2021113010204426600_B12","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.ahj.2007.01.002","article-title":"Associations of polymorphism of p22phox C242T, plasma levels of vitamin E, and smoking with coronary heart disease in China","volume":"153","author":"He","year":"2007","journal-title":"Am. Heart J."},{"key":"2021113010204426600_B13","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.cca.2009.12.018","article-title":"CYP1A1, CYP1A2 and CYBA gene polymorphisms associated with oxidative stress in COPD","volume":"411","author":"Vibhuti","year":"2010","journal-title":"Clin. Chim. Acta"},{"key":"2021113010204426600_B14","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1080\/026404197367362","article-title":"Oxidants, antioxidant nutrients and the athlete","volume":"15","author":"Packer","year":"1997","journal-title":"J. Sports Sci."},{"key":"2021113010204426600_B15","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.4238\/vol9-4gmr971","article-title":"GSTP1 Ile105Val polymorphism in astrocytomas and glioblastomas","volume":"9","author":"Cust\u00f3dio","year":"2010","journal-title":"Genet. Mol. Res."},{"key":"2021113010204426600_B16","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.bbrc.2007.05.076","article-title":"Genetic polymorphisms of GSTP1 and mEPHX correlate with oxidative stress markers and lung function in COPD","volume":"359","author":"Vibhuti","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021113010204426600_B17","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S0891-5849(99)00264-6","article-title":"Measurement of F2-isoprostanes as an index of oxidative stress in vivo","volume":"28","author":"Roberts","year":"2000","journal-title":"Free Radical Biol. Med."},{"key":"2021113010204426600_B18","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1056\/NEJM200107123450206","article-title":"High-altitude illness","volume":"345","author":"Hackett","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"2021113010204426600_B19","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1183\/09031936.95.08040523","article-title":"Pathogenesis of high-altitude pulmonary edema: direct evidence of stress failure of pulmonary capillaries","volume":"8","author":"West","year":"1995","journal-title":"Eur. Respir. J."},{"key":"2021113010204426600_B20","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1378\/chest.130.5.1511","article-title":"Heterozygotes of NOS3 polymorphisms contribute to reduced nitrogen oxides in high-altitude pulmonary edema","volume":"130","author":"Ahsan","year":"2006","journal-title":"Chest"},{"key":"2021113010204426600_B21","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1136\/thx.2006.066019","article-title":"Susceptibility to high-altitude pulmonary edema: roles of ACE and ET-1 polymorphisms","volume":"61","author":"Rajput","year":"2006","journal-title":"Thorax"},{"key":"2021113010204426600_B22","doi-asserted-by":"crossref","first-page":"10004","DOI":"10.1074\/jbc.272.15.10004","article-title":"Molecular cloning, characterization, and expression in Escherichia coli of full-length cDNAs of three human glutathione S-transferase \u03c0 gene variants. Evidence for differential catalytic activity of the encoded proteins","volume":"272","author":"Ali-Osman","year":"1997","journal-title":"J. Biol. Chem."},{"key":"2021113010204426600_B23","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1086\/319501","article-title":"A new statistical method for haplotype reconstruction from population data","volume":"68","author":"Stephan","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"2021113010204426600_B24","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1101\/gr.087577.108","article-title":"Signals of recent positive selection in a worldwide sample of human populations","volume":"19","author":"Pickrell","year":"2009","journal-title":"Genome Res."},{"key":"2021113010204426600_B25","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1152\/japplphysiol.00704.2003","article-title":"Pathophysiological significance of peroxidative stress, neuronal damage, and membrane permeability in acute mountain sickness","volume":"96","author":"Bailey","year":"2004","journal-title":"J. Appl. Physiol."},{"key":"2021113010204426600_B26","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1096\/fj.03-1077fje","article-title":"New aspects of altitude adaptation in Tibetans: a proteomic approach","volume":"18","author":"Gelfi","year":"2004","journal-title":"FASEB J."},{"key":"2021113010204426600_B27","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1378\/chest.06-2235","article-title":"Endogenous urate production augments plasma antioxidant capacity in healthy lowland subjects exposed to high altitude","volume":"131","author":"Baillie","year":"2007","journal-title":"Chest"},{"key":"2021113010204426600_B28","doi-asserted-by":"crossref","first-page":"4577","DOI":"10.1016\/j.febslet.2007.08.044","article-title":"Expression and functional activity of pro-oxidants and antioxidants in murine heart exposed to acute hypobaric hypoxia","volume":"581","author":"Karar","year":"2007","journal-title":"FEBS Lett."},{"key":"2021113010204426600_B29","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1046\/J.1469-1809.2005.00158.x","article-title":"Simultaneous selection of the wild type genotypes of the G894T and 4B\/4A polymorphisms of NOS3 associate with high altitude adaptation","volume":"69","author":"Ahsan","year":"2005","journal-title":"Ann. Hum. Genet."},{"key":"2021113010204426600_B30","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1016\/j.bbrc.2006.01.086","article-title":"Endothelin-1 gene variants and levels associate with adaptation to hypobaric hypoxia in high-altitude natives","volume":"341","author":"Rajput","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021113010204426600_B31","doi-asserted-by":"crossref","first-page":"18961","DOI":"10.1073\/pnas.1006108107","article-title":"EGLN1 involvement in high-altitude adaptation revealed through genetic analysis of extreme constitution types defined in Ayurveda","volume":"107","author":"Aggarwal","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113010204426600_B32","doi-asserted-by":"crossref","first-page":"S60","DOI":"10.1016\/j.placenta.2004.01.008","article-title":"Maternal adaptation to high-altitude pregnancy: an experiment of nature - a review","volume":"25","author":"Moore","year":"2004","journal-title":"Placenta"},{"key":"2021113010204426600_B33","doi-asserted-by":"crossref","first-page":"11459","DOI":"10.1073\/pnas.1002443107","article-title":"Natural selection on EPAS1 (HIF2\u03b1) associated with low hemoglobin concentration in Tibetan highlanders","volume":"107","author":"Beall","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113010204426600_B34","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1126\/science.1190371","article-title":"Sequencing of 50 human exomes reveals adaptation to high altitude","volume":"29","author":"Yi","year":"2010","journal-title":"Science"},{"key":"2021113010204426600_B35","doi-asserted-by":"crossref","first-page":"e1001116","DOI":"10.1371\/journal.pgen.1001116","article-title":"Identifying signatures of natural selection in Tibetan and Andean populations using dense genome scan data","volume":"6","author":"Bigham","year":"2010","journal-title":"PLoS Genet."},{"key":"2021113010204426600_B36","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1126\/science.1189406","article-title":"Genetic evidence for high-altitude adaptation in Tibet","volume":"329","author":"Simonson","year":"2010","journal-title":"Science"},{"key":"2021113010204426600_B37","first-page":"31","article-title":"Polymorphism \u2212930A &gt; G of the cytochrome b gene is a novel genetic marker of predisposition to bronchial asthma","volume":"81","author":"Polonikov","year":"2009","journal-title":"Ter. Arkh."},{"key":"2021113010204426600_B38","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1253\/circj.69.138","article-title":"Association analysis between hypertension and CYBA, CLCNKB, and KCNMB1 functional polymorphisms in the Japanese population\u2013the Suita Study","volume":"69","author":"Kokubo","year":"2005","journal-title":"Circ. J."},{"key":"2021113010204426600_B39","doi-asserted-by":"crossref","first-page":"640.e1","DOI":"10.1016\/j.ahj.2007.01.002","article-title":"Associations of polymorphism of p22phox C242T, plasma levels of vitamin E, and smoking with coronary heart disease in China","volume":"153","author":"He","year":"2007","journal-title":"Am. Heart J."},{"key":"2021113010204426600_B40","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1097\/01.hjh.0000234110.54110.56","article-title":"The C242T CYBA polymorphism of NADPH oxidase is associated with essential hypertension","volume":"24","author":"Moreno","year":"2006","journal-title":"J. Hypertens."},{"key":"2021113010204426600_B41","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.atherosclerosis.2006.12.007","article-title":"NAD(P)H oxidase polymorphism (C242T) and high HDL cholesterol associate with recurrent coronary events in postinfarction patients","volume":"196","author":"Corsetti","year":"2008","journal-title":"Atherosclerosis"},{"key":"2021113010204426600_B42","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.ahj.2006.02.018","article-title":"The p22phox C242T gene polymorphism is associated with a reduced risk of angiographically verified coronary artery disease in a high-risk Finnish Caucasian population. The Finnish Cardiovascular Study","volume":"152","author":"Fan","year":"2006","journal-title":"Am. Heart J."},{"key":"2021113010204426600_B43","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.atherosclerosis.2003.09.019","article-title":"Association of gene polymorphisms with coronary artery disease in individuals with or without nonfamilial hypercholesterolemia","volume":"172","author":"Shimokata","year":"2004","journal-title":"Atherosclerosis"},{"key":"2021113010204426600_B44","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1161\/01.CIR.97.2.135","article-title":"Polymorphism of the NADH\/NADPH Oxidase p22 phox Gene in Patients With Coronary Artery Disease","volume":"97","author":"Inoue","year":"1998","journal-title":"Circulation"},{"key":"2021113010204426600_B45","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s12013-011-9154-z","article-title":"Genetic polymorphisms of glutathione S-transferases are associated with ulcerative colitis in central China","volume":"60","author":"Ye","year":"2011","journal-title":"Cell Biochem. Biophys."},{"key":"2021113010204426600_B46","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/pcan.2010.54","article-title":"Glutathione S-transferase gene polymorphisms (GSTM1, GSTT1, GSTP1) and prostate cancer: a case-control study in Tehran, Iran","volume":"14","author":"Safarinejad","year":"2011","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"2021113010204426600_B47","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.canep.2010.07.003","article-title":"Genetic polymorphisms of glutathione S-transferase genes and susceptibility to colorectal cancer: a case-control study in an Indian population","volume":"35","author":"Wang","year":"2011","journal-title":"Cancer Epidemiol."},{"key":"2021113010204426600_B48","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1186\/2047-783X-14-S4-275","article-title":"Gene polymorphisms of biotransforming enzymes (GSTs) and their association with lung cancer in the Slovakian population","volume":"14","author":"Matakova","year":"2009","journal-title":"Eur. J. Med. Res."}],"container-title":["Clinical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/122\/6\/299\/441446\/cs1220299.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/122\/6\/299\/441446\/cs1220299.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,10]],"date-time":"2023-06-10T09:25:10Z","timestamp":1686389110000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/clinsci\/article\/122\/6\/299\/68964\/CYBA-and-GSTP1-variants-associate-with-oxidative"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,11,22]]},"references-count":48,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2012,3,1]]}},"URL":"https:\/\/doi.org\/10.1042\/cs20110205","relation":{},"ISSN":["0143-5221","1470-8736"],"issn-type":[{"value":"0143-5221","type":"print"},{"value":"1470-8736","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,11,22]]}}}