{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:01:03Z","timestamp":1791475263459,"version":"4.3.4"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T00:00:00Z","timestamp":1662076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Branched-Chain Amino Acids (BCAAs) has been identified as a risk factor for circulatory disease. Nevertheless, the effects and mechanisms of BCAAs on the risk of moyamoya disease (MMD) remain unrecognized. Hence, we aimed to elucidate the association between circulating BCAAs and the risk of MMD and clinical subtypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a case-control study of 360 adult MMD patients and 89 matched healthy controls consecutively recruited between September 2020 and December 2021. Serum level of BCAAs was quantified by liquid chromatography-mass spectrometry. The associations between BCAAs and risk of MMD were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Increased level of serum BCAAs was observed in MMD patients (<jats:italic>P<\/jats:italic> &amp;lt; 0.001). After adjusting for traditional confounders, the elevated BCAAs level was significantly associated with the risk of MMD (Q4 vs. Q1: odds ratio, 3.10 [95% CI, 1.29\u20137.50]). The risk of subtypes in MMD also increased with each increment in the quartiles of BCAAs. Furthermore, BCAAs offered substantial improvement in risk reclassification and discrimination for MMD and subtypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Higher level of circulating BCAAs was associated with increased risk of MMD and clinical subtypes. This study will help to elucidate the pathogenesis of MMD, which may provide the support for facilitating the treatments and preventions.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2022.994286","type":"journal-article","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T10:08:57Z","timestamp":1662113337000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Association of circulating branched-chain amino acids with risk of moyamoya disease"],"prefix":"10.3389","volume":"9","author":[{"given":"Chaofan","family":"Zeng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peicong","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenglong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanren","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiheng","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junsheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingju","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jizong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,2]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","DOI":"10.2176\/jns-nmc.2021-0382","article-title":"2021 Japanese Guidelines for the Management of Moyamoya Disease: guidelines from the Research Committee on Moyamoya Disease and Japan Stroke Society","volume-title":"Neurol. Med. Chir. (Tokyo)","author":"Fujimura","year":""},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S1474-4422(22)00165-X","article-title":"Moyamoya disease : diagnosis and interventions","volume":"4422","author":"Ihara","year":"2022","journal-title":"Lancet Neurol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.3171\/2016.2.JNS152173","article-title":"RNF213 as the major susceptibility gene for Chinese patients with moyamoya disease and its clinical relevance","volume":"126","author":"Zhang","year":"2017","journal-title":"J Neurosurg."},{"key":"B4","article-title":"Association of RNF213 variants with periventricular anastomosis in moyamoya disease","volume-title":"Stroke.","author":"Xue","year":"2022"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2472","DOI":"10.1161\/STROKEAHA.120.030027","article-title":"Modifiable risk factors associated with moyamoya disease: a case-control study","volume":"51","author":"Ge","year":"2020","journal-title":"Stroke."},{"key":"B6","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1038\/s41582-020-0350-6","article-title":"Multilevel omics for the discovery of biomarkers and therapeutic targets for stroke","volume":"16","author":"Montaner","year":"2020","journal-title":"Nat Rev Neurol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1146\/annurev-physiol-020518-114455","article-title":"Branched chain amino acids","volume":"81","author":"Neinast","year":"2019","journal-title":"Annu Rev Physiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1038\/nrendo.2014.171","article-title":"Branched-chain amino acids in metabolic signalling and insulin resistance","volume":"10","author":"Lynch","year":"2014","journal-title":"Nat Rev Endocrinol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.atherosclerosis.2022.04.026","article-title":"Association of circulating branched-chain amino acids with risk of cardiovascular disease : a systematic review and meta-analysis","volume":"350","author":"Wang","year":"2022","journal-title":"Atherosclerosis."},{"key":"B10","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.ccell.2019.12.011","article-title":"Emerging roles for branched-chain amino acid metabolism in cancer","volume":"37","author":"Sivanand","year":"2020","journal-title":"Cancer Cell."},{"key":"B11","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1007\/s00726-021-03100-w","article-title":"Targeted metabolomics analysis of serum amino acid profiles in patients with Moyamoya disease","volume":"54","author":"Liu","year":"2022","journal-title":"Amino Acids."},{"key":"B12","doi-asserted-by":"publisher","first-page":"308","DOI":"10.3389\/fnins.2020.00308","article-title":"Metabolomic profiling revealed potential biomarkers in patients with moyamoya disease","volume":"14","author":"Geng","year":"2020","journal-title":"Front Neurosci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/s41580-021-00411-4","article-title":"Molecular mechanisms of dietary restriction promoting health and longevity","volume":"23","author":"Green","year":"2022","journal-title":"Nat Rev Mol Cell Biol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.cmet.2018.10.013","article-title":"Quantitative analysis of the whole-body metabolic fate of branched-chain amino acids","volume":"29","author":"Neinast","year":"2019","journal-title":"Cell Metab."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1002\/oby.20691","article-title":"Alloisoleucine differentiates the branched-chain aminoacidemia of Zucker and dietary obese rats","volume":"22","author":"Olson","year":"2014","journal-title":"Obesity (Silver Spring)."},{"key":"B16","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1373\/clinchem.2015.251710","article-title":"Plasma branched-chain amino acids and incident cardiovascular disease in the PREDIMED Trial","volume":"62","author":"Ruiz-Canela","year":"2016","journal-title":"Clin Chem."},{"key":"B17","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1007\/s00125-015-3517-8","article-title":"Diabetes risk and amino acid profiles: cross-sectional and prospective analyses of ethnicity, amino acids and diabetes in a South Asian and European cohort from the SABRE (Southall And Brent REvisited) Study","volume":"58","author":"Tillin","year":"2015","journal-title":"Diabetologia."},{"key":"B18","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.atherosclerosis.2021.09.011","article-title":"The metabolomic profile of carotid artery intima-media thickness and echogenicity","volume":"335","author":"Lind","year":"2021","journal-title":"Atherosclerosis."},{"key":"B19","article-title":"Mitochondrial H2S regulates BCAA catabolism in heart failure","volume-title":"Circ Res.","author":"Li","year":"2022"},{"key":"B20","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.cmet.2016.11.005","article-title":"Defective branched-chain amino acid catabolism disrupts glucose metabolism and sensitizes the heart to ischemia-reperfusion injury","volume":"25","author":"Li","year":"2017","journal-title":"Cell Metab."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1980","DOI":"10.1161\/HYPERTENSIONAHA.120.15236","article-title":"Mitochondrial isolevuglandins contribute to vascular oxidative stress and mitochondria-targeted scavenger of isolevuglandins reduces mitochondrial dysfunction and hypertension","volume":"76","author":"Dikalova","year":"2020","journal-title":"Hypertens. (Dallas, Tex. 1979)"},{"key":"B22","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1159\/000442298","article-title":"Research progresses in understanding the pathophysiology of moyamoya disease","volume":"41","author":"Bersano","year":"2016","journal-title":"Cerebrovasc Dis."},{"key":"B23","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.redox.2016.08.015","article-title":"Redox signaling in cardiovascular pathophysiology: A focus on hydrogen peroxide and vascular smooth muscle cells","volume":"9","author":"Byon","year":"2016","journal-title":"Redox Biol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.3171\/2017.5.JNS17147","article-title":"Mitochondrial abnormalities related to the dysfunction of circulating endothelial colony-forming cells in moyamoya disease","volume":"129","author":"Choi","year":"2018","journal-title":"J Neurosurg."},{"key":"B25","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1016\/j.bbalip.2011.09.009","article-title":"Phosphatidylcholine biosynthesis and lipoprotein metabolism","volume":"1821","author":"Cole","year":"2012","journal-title":"Biochim Biophys Acta."},{"key":"B26","doi-asserted-by":"publisher","first-page":"2221","DOI":"10.1021\/acs.jproteome.7b00030","article-title":"Effects of histidine supplementation on global serum and urine 1H NMR-based metabolomics and serum amino acid profiles in obese women from a randomized controlled study","volume":"16","author":"Du","year":"2017","journal-title":"J Proteome Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.freeradbiomed.2017.01.009","article-title":"High concentration of branched-chain amino acids promotes oxidative stress, inflammation and migration of human peripheral blood mononuclear cells via mTORC1 activation","volume":"104","author":"Zhenyukh","year":"2017","journal-title":"Free Radic Biol Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/s11011-020-00616-0","article-title":"Circulating sortilin levels are associated with inflammation in patients with moyamoya disease","volume":"36","author":"Han","year":"2021","journal-title":"Metab Brain Dis."},{"key":"B29","doi-asserted-by":"publisher","first-page":"5847478","DOI":"10.1155\/2020\/5847478","article-title":"Association of brain-gut peptides with inflammatory cytokines in moyamoya disease","volume":"2020","author":"Han","year":"2020","journal-title":"Mediat Inflamm."},{"key":"B30","doi-asserted-by":"publisher","first-page":"E20","DOI":"10.3171\/2011.3.FOCUS1151","article-title":"Moyamoya disease: a review of histopathology, biochemistry, and genetics","volume":"30","author":"Weinberg","year":"2011","journal-title":"Neurosurg Focus."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1960","DOI":"10.1161\/01.STR.24.12.1960","article-title":"Smooth muscle cell proliferation and localization of macrophages and t cells in the occlusive intracranial major arteries in moyamova disease","volume":"24","author":"Masuda","year":"1993","journal-title":"Stroke."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1016\/j.cmet.2018.04.015","article-title":"The BCKDH kinase and phosphatase integrate BCAA and lipid metabolism via regulation of ATP-citrate lyase","volume":"27","author":"White","year":"2018","journal-title":"Cell Metab."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.21037\/atm-20-624a","article-title":"Branched-chain amino acids are linked with iron metabolism","volume":"8","author":"Enko","year":"2020","journal-title":"Ann Transl Med."},{"key":"B34","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1016\/j.cmet.2021.03.025","article-title":"The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine","volume":"33","author":"Yu","year":"2021","journal-title":"Cell Metab."},{"key":"B35","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/j.nicl.2018.03.028","article-title":"Which of the branched-chain amino acids increases cerebral blood flow in hepatic encephalopathy? A double-blind randomized trial","volume":"19","author":"Romeiro","year":"2018","journal-title":"NeuroImage Clin."}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.994286\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T10:09:04Z","timestamp":1662113344000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.994286\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,2]]},"references-count":35,"alternative-id":["10.3389\/fnut.2022.994286"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2022.994286","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,2]]},"article-number":"994286"}}