{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T16:01:37Z","timestamp":1740153697760,"version":"3.37.3"},"reference-count":61,"publisher":"Wiley","license":[{"start":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T00:00:00Z","timestamp":1618185600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015690","name":"Universitas Padjadjaran","doi-asserted-by":"publisher","award":["2476\/UN6.C\/LT\/2018"],"award-info":[{"award-number":["2476\/UN6.C\/LT\/2018"]}],"id":[{"id":"10.13039\/501100015690","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["International Journal of Dentistry"],"published-print":{"date-parts":[[2021,4,12]]},"abstract":"<jats:p>Objective. To investigate the DNA methylation using pyrosequencing and its effects on the upregulation of IL6 mRNA in patients with recurrent aphthous stomatitis (RAS) in connection with hematinic deficiency and atopy. Material and Methods. This cross-sectional study was conducted at Dr. Hasan Sadikin Hospital, Bandung, from January\u2013March 2019 and was approved by the Health Research Ethics Committee of Universitas Padjadjaran (Ethics No. 990\/UN6.KEP\/EC\/2018). Furthermore, the subjects had RAS ulcers with a history of at least twice a year along with atopy and dietary imbalance with no history of recurrent intraoral herpes or any systemic diseases. This study was performed on 23 RAS patients and 21 healthy subjects, and the sampling was carried out consecutively. The blood samples were collected from all the subjects, and then, the DNA and RNA were extracted from the peripheral blood mononuclear cells (PBMCs). Consequently, the bisulfite-modified DNA was used to confirm the methylation status of the IL6 gene promoter through the pyrosequencing method. The methylation levels of the IL6 promoter were assessed by a reverse transcriptase-polymerase chain reaction technique. The gene expression of RAS and the control group was analyzed by the 2\u2212\u0394\u0394CT method. The statistical analysis using the Mann\u2013Whitney U test was conducted to evaluate IL6 mRNA levels and DNA methylation with<jats:inline-formula><a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><a:mi>p<\/a:mi><\/a:math><\/jats:inline-formula>value &lt;0.05 considered to be statistically significant. Result. The IL6 mRNA levels were approximately 1.88-fold in RAS patients, and there was a significant relationship between the expression of the IL6 gene and the increased risk of RAS<jats:inline-formula><c:math xmlns:c=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><c:mfenced open=\"(\" close=\")\" separators=\"|\"><c:mrow><c:mi>p<\/c:mi><c:mo>&lt;<\/c:mo><c:mn>0.001<\/c:mn><\/c:mrow><\/c:mfenced><\/c:math><\/jats:inline-formula>. It was reported that four out of six sites in the cytosine phosphate guanine (CpG) island IL6 promoter had a lower degree of methylation, and two other sites in patients with RAS had greater methylation compared with control, but not statistically significant. Conclusion. This study showed the upregulation of IL6 mRNA levels in RAS patients compared to control. DNA methylation in the present study is at sites 566\u2013658, whereas the location of the IL6 promoter is at sites 1\u20131684. Thus, it would be necessary conducting some research at other CpG sites of IL6 promoter islands to determine the status of DNA methylation.<\/jats:p>","DOI":"10.1155\/2021\/5560695","type":"journal-article","created":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T19:20:22Z","timestamp":1618255222000},"page":"1-11","source":"Crossref","is-referenced-by-count":3,"title":["The Impact of DNA Methylation on IL6 mRNA Levels in Hematinic Deficiency and Atopy-Associated Recurrent Aphthous Stomatitis Patients"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2652-2953","authenticated-orcid":true,"given":"Nanan","family":"Nur\u2019aeny","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0714-7772","authenticated-orcid":true,"given":"Dida Akhmad","family":"Gurnida","sequence":"additional","affiliation":[{"name":"Child Health Department, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4017-9319","authenticated-orcid":true,"given":"Oki","family":"Suwarsa","sequence":"additional","affiliation":[{"name":"Dermatology and Venereal Disease Department, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2506-5105","authenticated-orcid":true,"given":"Irna","family":"Sufiawati","sequence":"additional","affiliation":[{"name":"Oral Medicine Department, Faculty of Dentistry, Universitas Padjadjaran, Bandung, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.24198\/pjd.vol32no3.23664"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.24198\/pjdrs.v2i1.22112"},{"issue":"5","key":"3","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1590\/abd1806-4841.20174692","article-title":"Recurrent aphthous stomatitis in 18-year-old adolescents-prevalence and associated factors: a population-based study","volume":"92","author":"P. Ricardo","year":"2017","journal-title":"Anais Brasileiros de Dermatologia"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.5152\/balkanmedj.2016.15101"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.15386\/cjmed-840"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/2907812"},{"issue":"2","key":"7","doi-asserted-by":"crossref","first-page":"96","DOI":"10.5114\/pdia.2013.34158","article-title":"Recurrent aphthous stomatitis: genetic aspects of etiology","volume":"2","author":"Z. \u015alebioda","year":"2013","journal-title":"Post\u0119py Dermatologii I Alergol"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1177\/2229411220140301"},{"issue":"2","key":"9","first-page":"124","article-title":"Haematological parameters and recurrent aphthous stomatitis","volume":"23","author":"N. F. Khan","year":"2013","journal-title":"Journal of College of Physicians and Surgeons Pakistan"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfma.2016.10.007"},{"issue":"3","key":"11","first-page":"144","article-title":"Expression of pathergy in atopics","volume":"15","author":"C. Veller-Fornasa","year":"2006","journal-title":"Acta Dermatoven APA"},{"first-page":"41","article-title":"Correlation between oral lesion and total serum IgE level in atopic patient","author":"N. Nur\u2019aeny","key":"12"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.4103\/2229-3019.166117"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.8.1225"},{"issue":"10","key":"15","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1111\/jop.12594","article-title":"Association study of interleukin-1 family, interleukin-6 and its receptor gene polymorphisms in patients with recurrent aphthous stomatitis","volume":"46","author":"I. H. Lydie","year":"2017","journal-title":"Journal of Oral Pathology and Medicine"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1111\/iji.12228"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1111\/jop.12621"},{"key":"18","first-page":"4","article-title":"The emerging role of the type 2 inflammatory cascade in atopic diseases","volume":"25","author":"S. V. President","year":"2010","journal-title":"The American Journal of Managed Care"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1080\/1744666X.2017.1298443"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.3402\/ecrj.v2.24642"},{"key":"21","first-page":"1","article-title":"Elevation of IL-6 in the allergic asthmatic airway is independent of inflammation but associates with loss of central airway function","volume":"11","author":"M. Rincon","year":"2010","journal-title":"Respiratory Research"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1016\/j.arbr.2016.11.006"},{"issue":"2","key":"23","first-page":"89","article-title":"Association between the interleukin 6 genotype at position-174 and atopic dermatitis","volume":"23","author":"M. Gharagozlou","year":"2013","journal-title":"Journal of Investigational Allergology and Clinical Immunology"},{"issue":"1","key":"24","doi-asserted-by":"crossref","first-page":"20","DOI":"10.24198\/pjd.vol31no1.21223","article-title":"Serum IL-6 levels of atopic patients with recurrent aphthous stomatitis (RAS)","volume":"31","author":"N. Nur\u2019aeny","year":"2019","journal-title":"Padjadjaran Journal of Dentistry"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1016\/j.aller.2013.11.006"},{"issue":"2","key":"26","first-page":"268","article-title":"Role of interleukin-6 in immunity\u202f: a review","volume":"4","author":"S. Naseem","year":"2016","journal-title":"International Journal Life Sciences"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2006.08.008"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gene.6363882"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.1007\/s00403-013-1406-x"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.1016\/j.otc.2010.09.007"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.1016\/j.adaj.2017.02.028"},{"key":"32","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.10.039"},{"key":"33","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1201\/9781420063561.ch10","volume-title":"Nutrients Epigenetics","author":"S. Choi","year":"2009"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.1016\/j.jada.2008.06.430"},{"issue":"3","key":"35","first-page":"88","article-title":"Prevalence of hematinics defi ciency amongst female students and its correction","volume":"23","author":"B. C. M. R. M. K. Y. Patel","year":"2018","journal-title":"Indian Journal of Hematology and Blood Transfusion"},{"key":"36","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-015-0154-5"},{"key":"37","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq537"},{"key":"38","doi-asserted-by":"crossref","first-page":"376","DOI":"10.5772\/2205","volume-title":"Gel Electrophoresis-Principles and Basics","author":"S. Magdeldin","year":"2012"},{"key":"39","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.21762"},{"key":"40","article-title":"Good practice guide for the application of quantitative PCR (qPCR)","volume":"50","author":"T. Nolan","year":"2013","journal-title":"National Measurement System"},{"key":"41","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"issue":"3","key":"42","first-page":"71","article-title":"An improvement of the 2\u02c6(-delta delta CT) method for quantitative real-time polymerase chain reaction data analysis","volume":"3","author":"X. Rao","year":"2013","journal-title":"Biostat Bioinforma Biomath"},{"key":"43","doi-asserted-by":"publisher","DOI":"10.14348\/molcells.2015.0005"},{"key":"44","doi-asserted-by":"publisher","DOI":"10.3390\/nu12020461"},{"key":"45","doi-asserted-by":"publisher","DOI":"10.3390\/nu11030608"},{"issue":"1","key":"46","doi-asserted-by":"crossref","first-page":"36","DOI":"10.4317\/jced.51227","article-title":"Prevalence of recurrent aphthous ulceration in the Indian Population","volume":"6","author":"S. Patil","year":"2014","journal-title":"Journal of Clinical and Experimental Dentistry"},{"issue":"2","key":"47","doi-asserted-by":"crossref","first-page":"196","DOI":"10.5114\/ada.2018.74638","article-title":"Systemic and environmental risk factors for recurrent Aphthous stomatitis in a polish cohort of patients","volume":"36","author":"Z. \u015alebioda","year":"2019","journal-title":"Postep Dermatologii I Alergologii"},{"issue":"3","key":"48","doi-asserted-by":"crossref","first-page":"286","DOI":"10.5614\/j.math.fund.sci.2020.52.3.3","article-title":"Serum level of IL-6 , reactive oxygen species and cortisol in patients with recurrent aphthous stomatitis related imbalance nutrition intake and atopy","volume":"53","author":"N. Nur\u2019aeny","year":"2020","journal-title":"Journal of Mathematical and Fundamental Sciences"},{"key":"49","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/hct051"},{"key":"50","doi-asserted-by":"publisher","DOI":"10.4317\/medoral.21885"},{"issue":"4","key":"51","first-page":"872","article-title":"Hematologic abnormalities in recurrent oral","volume":"33","author":"K. Thongprasom","year":"2002","journal-title":"Southeast Asian Journal of Tropical Medicine and Public Health"},{"key":"52","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.09.059"},{"key":"53","doi-asserted-by":"publisher","DOI":"10.4103\/0970-2113.63609"},{"issue":"10","key":"54","doi-asserted-by":"crossref","DOI":"10.5005\/jp-journals-10024-2411","article-title":"Establishment of role of IL-2, IL-10 and IL-12 in patients with recurrent aphthous stomatitis-a clinical study","volume":"19","author":"S. S. Bhosale","year":"2018","journal-title":"Journal of Contemporary Dental Practice"},{"key":"55","doi-asserted-by":"publisher","DOI":"10.1089\/gtmb.2017.0072"},{"key":"56","doi-asserted-by":"publisher","DOI":"10.1186\/s12903-019-0993-0"},{"key":"57","doi-asserted-by":"publisher","DOI":"10.1576\/toag.12.1.037.27556"},{"key":"58","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3230"},{"key":"59","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/132.8.2382S"},{"key":"60","doi-asserted-by":"publisher","DOI":"10.3945\/jn.109.113670"},{"key":"61","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/132.12.3814s"}],"container-title":["International Journal of Dentistry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/ijd\/2021\/5560695.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ijd\/2021\/5560695.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ijd\/2021\/5560695.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T00:27:17Z","timestamp":1698884837000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/ijd\/2021\/5560695\/"}},"subtitle":[],"editor":[{"given":"Amol","family":"Gadbail","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,4,12]]},"references-count":61,"alternative-id":["5560695","5560695"],"URL":"https:\/\/doi.org\/10.1155\/2021\/5560695","relation":{},"ISSN":["1687-8736","1687-8728"],"issn-type":[{"type":"electronic","value":"1687-8736"},{"type":"print","value":"1687-8728"}],"subject":[],"published":{"date-parts":[[2021,4,12]]}}}