{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T14:23:13Z","timestamp":1760710993012,"version":"3.40.5"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T00:00:00Z","timestamp":1659052800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Vitiligo is one of the most common hypomelanoses, in which the destruction of functioning melanocytes causes depigmentation of the skin, hair and mucous membranes. The genes encrypting brain-derived neurotrophic factor (BDNF) and corticotropin releasing hormone (CRH) might be the conceivable contributors to the development of vitiligo. This study was aimed at investigation of the serum levels of BDNF and CRH as well as their selected single nucleotide polymorphisms (SNPs) in vitiligo patients in comparison with the healthy controls.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>The cross-sectional study was carried out between October 2020 and June 2021 in 93 vitiligo patients (age range from 23 to 48 years) and 132 healthy controls (age range from 24 to 52 years). The psychological status of study participants was evaluated using the Generalized Anxiety Disorder-7 (GAD-7) scale. Serum levels of BDNF and CRH were measured with the help of a commercially available sandwich enzyme-linked immunosorbent assay (ELISA) kit. Genotyping for the rs11030094 polymorphism of the <jats:italic>BDNF<\/jats:italic> gene and for the rs242924 polymorphism of the corticotropin releasing hormone receptor 1 <jats:italic>(CRH-R1)<\/jats:italic> gene was performed by a real-time polymerase chain reaction (PCR).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>There was a significant relationship between the <jats:italic>CRH-R1<\/jats:italic> rs242924 and <jats:italic>BDNF<\/jats:italic> rs11030094 polymorphisms and vitiligo. Moreover, serum levels of neurotransmitters differed significantly between vitiligo and control groups and were associated with the <jats:italic>CRH-R1<\/jats:italic> rs242924 and <jats:italic>BDNF<\/jats:italic> rs11030094 SNPs.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Our findings demonstrated the association between <jats:italic>CRH-R1<\/jats:italic> rs242924 and <jats:italic>BDNF<\/jats:italic> rs11030094 polymorphisms and vitiligo. Further studies need to be carried out in vitiligo patients to confirm the results observed.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0271719","type":"journal-article","created":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T17:34:25Z","timestamp":1659116065000},"page":"e0271719","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Gene polymorphisms and serum levels of BDNF and CRH in vitiligo patients"],"prefix":"10.1371","volume":"17","author":[{"given":"Assiya","family":"Kussainova","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4448-6455","authenticated-orcid":true,"given":"Laura","family":"Kassym","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nazira","family":"Bekenova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Almira","family":"Akhmetova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalya","family":"Glushkova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Almas","family":"Kussainov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhanar","family":"Urazalina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oxana","family":"Yurkovskaya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yerbol","family":"Smail","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Pak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuliya","family":"Semenova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,7,29]]},"reference":[{"issue":"2","key":"pone.0271719.ref001","doi-asserted-by":"crossref","first-page":"96","DOI":"10.5144\/0256-4947.2022.96","article-title":"Association of genetic variants of the vitamin D receptor gene with vitiligo in a tertiary care center in a Saudi population: a case-control study.","volume":"42","author":"GB Saif","year":"2022","journal-title":"Ann Saudi Med"},{"issue":"5","key":"pone.0271719.ref002","first-page":"e8046","article-title":"Associations of Angiotensin-Converting Enzyme Gene Insertion\/Deletion (ACE Gene I\/D) Polymorphism With Vitiligo: An Updated Systematic Review and Meta-Analysis","volume":"12","author":"M. 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A. Spritz","year":"2011","journal-title":"Journal of Investigative Dermatology"},{"issue":"1","key":"pone.0271719.ref008","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/pcmr.12848","article-title":"The genetic architecture of vitiligo","volume":"33","author":"GHL Roberts","year":"2020","journal-title":"Pigment Cell Melanoma Res"},{"issue":"2","key":"pone.0271719.ref009","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1055\/s-2007-961812","article-title":"Neurotrophins act as neuroendocrine regulators of skin homeostasis in health and disease","volume":"39","author":"E. M. 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Ishitobi","year":"2012","journal-title":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics"},{"issue":"2","key":"pone.0271719.ref028","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s00213-012-2956-x","article-title":"Genetic association of FKBP5 and CRHR1 with cortisol response to acute psychosocial stress in healthy adults","volume":"227","author":"PB Mahon","year":"2013","journal-title":"Psychopharmacology (Berl)."},{"issue":"9","key":"pone.0271719.ref029","doi-asserted-by":"crossref","first-page":"e42450","DOI":"10.1371\/journal.pone.0042450","article-title":"Corticotropin-releasing hormone receptor 1 gene variants in irritable bowel syndrome.","volume":"7","author":"N Sato","year":"2012","journal-title":"PLoS One."},{"issue":"2","key":"pone.0271719.ref030","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s00403-012-1218-4","article-title":"The association of PASI scores with CRH-R1 expression in patients with psoriasis","volume":"304","author":"BC Cemil","year":"2012","journal-title":"Arch Dermatol Res"},{"issue":"5","key":"pone.0271719.ref031","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1111\/j.0022-202X.2005.23913.x","article-title":"Corticotropin-releasing hormone receptor-1 and histidine decarboxylase expression in chronic urticaria","volume":"125","author":"N Papadopoulou","year":"2005","journal-title":"J Invest Dermatol"},{"issue":"2","key":"pone.0271719.ref032","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1159\/000329592","article-title":"Association of hypothalamic-pituitary-adrenal axis-related polymorphisms with stress in asthmatic children on inhaled corticosteroids","volume":"19","author":"L Tsartsali","year":"2012","journal-title":"Neuroimmunomodulation"},{"issue":"1","key":"pone.0271719.ref033","doi-asserted-by":"crossref","first-page":"7260","DOI":"10.1038\/s41598-022-11028-8","article-title":"Associations between serum levels of brain-derived neurotrophic factor, corticotropin releasing hormone and mental distress in vitiligo patients.","volume":"12","author":"A Kussainova","year":"2022","journal-title":"Sci Rep."},{"issue":"1","key":"pone.0271719.ref034","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.mcp.2008.10.005","article-title":"Variation in the BDNF and NGFB genes in German atopic dermatitis patients","volume":"23","author":"S Hoffjan","year":"2009","journal-title":"Mol Cell Probes"},{"issue":"10","key":"pone.0271719.ref035","doi-asserted-by":"crossref","first-page":"7015","DOI":"10.1007\/s11033-014-3589-4","article-title":"Combined effects of the BDNF rs6265 (Val66Met) polymorphism and environment risk factors on psoriasis vulgaris.","volume":"41","author":"C Quan","year":"2014","journal-title":"Mol Biol Rep"},{"issue":"5","key":"pone.0271719.ref036","doi-asserted-by":"crossref","first-page":"43","DOI":"10.14715\/cmb\/2019.65.5.7","article-title":"Interleukin-6 serum level and gene polymorphism in keloid patients","volume":"65","author":"AMK Abdu Allah","year":"2019","journal-title":"Cell Mol Biol (Noisy-le-grand)."},{"issue":"1","key":"pone.0271719.ref037","doi-asserted-by":"crossref","first-page":"1951291","DOI":"10.1080\/15321819.2021.1952425","article-title":"Interleukin19 gene polymorphism and its serum level in acne vulgaris patients","volume":"43","author":"H Bazid","year":"2022","journal-title":"J Immunoassay Immunochem"},{"key":"pone.0271719.ref038","doi-asserted-by":"crossref","first-page":"146027","DOI":"10.1016\/j.gene.2021.146027","article-title":"Meta-analysis for association of TNFA-308(G > A) SNP with vitiligo susceptibility.","volume":"809","author":"PS Giri","year":"2022","journal-title":"Gene"},{"issue":"9","key":"pone.0271719.ref039","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1111\/ijd.12866","article-title":"The association between tumor necrosis factor-\u03b1-308 G\/A polymorphism and risk for vitiligo: a 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