{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:09:36Z","timestamp":1790662176858,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T00:00:00Z","timestamp":1596153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Austrian Science Fund (FWF)","award":["P32470, F4701-B20 and F4704-B20"],"award-info":[{"award-number":["P32470, F4701-B20 and F4704-B20"]}]},{"name":"Polish Ministry of Sciences and Education","award":["ST 02-0066\/07\/253 and ST 02-0141\/07\/231"],"award-info":[{"award-number":["ST 02-0066\/07\/253 and ST 02-0141\/07\/231"]}]},{"name":"Polish Ministry of Science","award":["DIR\/WK\/2017\/01"],"award-info":[{"award-number":["DIR\/WK\/2017\/01"]}]},{"name":"Popoulous collection founded by European Regional Development Fund","award":["POIG Grant 01.01.02-10-005\/08 TESTOPLEK"],"award-info":[{"award-number":["POIG Grant 01.01.02-10-005\/08 TESTOPLEK"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mastocytosis is rare disease in which genetic predisposition is not fully understood. The aim of this study was to analyze associations between mastocytosis and single nucleotide polymorphisms (SNPs) by a genome-wide association study (GWAS) approach. A total of 234 patients were enrolled in our study, including 141 with cutaneous mastocytosis (CM; 78 children and 63 adults) and 93 with systemic mastocytosis (SM, all adults). The control group consisted of 5606 healthy individuals. DNA samples from saliva or blood were genotyped for 551 945 variants using DNA microarrays. The prevalence of certain SNPs was found to vary substantially when comparing patients and healthy controls: rs10838094 of 5OR51Q1 was less frequently detected in CM and SM patients (OR = 0.2071, p = 2.21 \u00d7 10\u221229), rs80138802 in ABCA2 (OR = 5.739, p = 1.98 \u00d7 10\u221228), and rs11845537 in OTX2-AS1 (rs11845537, OR = 6.587, p = 6.16 \u00d7 10\u221217) were more frequently detected in CM in children and adults. Additionally, we found that rs2279343 in CYP2B6 and rs7601511 in RPTN are less prevalent in CM compared to controls. We identified a number of hitherto unknown associations between certain SNPs and CM and\/or SM. Whether these associations are clinically relevant concerning diagnosis, prognosis, or prevention remains to be determined in future studies.<\/jats:p>","DOI":"10.3390\/ijms21155506","type":"journal-article","created":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T06:16:47Z","timestamp":1596435407000},"page":"5506","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Results from a Genome-Wide Association Study (GWAS) in Mastocytosis Reveal New Gene Polymorphisms Associated with WHO Subgroups"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6286-0693","authenticated-orcid":false,"given":"Bogus\u0142aw","family":"Nedoszytko","sequence":"first","affiliation":[{"name":"Department of Dermatology, Venerology and Allergology, Medical University of Gdansk, 80-211 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Sobalska-Kwapis","sequence":"additional","affiliation":[{"name":"Biobank Laboratory, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 90-237 Lodz, Poland"},{"name":"Biobanking &amp; Molecular Biotechnologies Resources Infrastructures Poland (BBMRI.pl) Consortium, 50-367 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9752-4270","authenticated-orcid":false,"given":"Dominik","family":"Strapagiel","sequence":"additional","affiliation":[{"name":"Biobank Laboratory, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 90-237 Lodz, Poland"},{"name":"Biobanking &amp; Molecular Biotechnologies Resources Infrastructures Poland (BBMRI.pl) Consortium, 50-367 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Lange","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venerology and Allergology, Medical University of Gdansk, 80-211 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"G\u00f3rska","sequence":"additional","affiliation":[{"name":"Department of Allergology, Medical University of Gdansk, 80-211 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2844-2196","authenticated-orcid":false,"given":"Joanne N. G. Oude","family":"Elberink","sequence":"additional","affiliation":[{"name":"Department of Allergology, Internal Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper","family":"van Doormaal","sequence":"additional","affiliation":[{"name":"Department of Allergology, Internal Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"S\u0142omka","sequence":"additional","affiliation":[{"name":"Biobank Laboratory, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 90-237 Lodz, Poland"},{"name":"Biobanking &amp; Molecular Biotechnologies Resources Infrastructures Poland (BBMRI.pl) Consortium, 50-367 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leszek","family":"Kalinowski","sequence":"additional","affiliation":[{"name":"Biobanking &amp; Molecular Biotechnologies Resources Infrastructures Poland (BBMRI.pl) Consortium, 50-367 Wroc\u0142aw, Poland"},{"name":"Department of Medical Laboratory Diagnostics, Medical University of Gdansk, 80-211 Gdansk, Poland"},{"name":"Department of Mechanics of Materials and Structures, Gdansk University of Technology, 80-223 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Grucha\u0142a-Niedoszytko","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, Medical University of Gdansk, 80-211 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4768-1387","authenticated-orcid":false,"given":"Roman J.","family":"Nowicki","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venerology and Allergology, Medical University of Gdansk, 80-211 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0456-5095","authenticated-orcid":false,"given":"Peter","family":"Valent","sequence":"additional","affiliation":[{"name":"Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, 18-20 Vienna, Austria"},{"name":"Ludwig Boltzmann Institute for Hematology &amp; Oncology, Medical University of Vienna, Medical University of Vienna, Waehringer Guertel, 18-20 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Niedoszytko","sequence":"additional","affiliation":[{"name":"Department of Allergology, Medical University of Gdansk, 80-211 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/S0145-2126(01)00038-8","article-title":"Diagnostic criteria and classification of mastocytosis: A consensus proposal","volume":"25","author":"Valent","year":"2001","journal-title":"Leuk Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1111\/j.1365-2362.2007.01807.x","article-title":"Standards and standardization in mastocytosis: Consensus statements on diagnostics, treatment recommendations and response criteria","volume":"37","author":"Valent","year":"2007","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1158\/0008-5472.CAN-16-2234","article-title":"Advances in the Classification and Treatment of Mastocytosis: Current Status and Outlook toward the Future","volume":"77","author":"Valent","year":"2017","journal-title":"Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1182\/blood-2016-09-731893","article-title":"Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts","volume":"129","author":"Valent","year":"2017","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.jaci.2015.08.034","article-title":"Cutaneous manifestations in patients with mastocytosis: Consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology","volume":"137","author":"Hartmann","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1056\/NEJMra1409760","article-title":"Mast Cells, Mastocytosis, and Related Disorders","volume":"373","author":"Theoharides","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1038\/leu.2015.24","article-title":"KIT mutation analysis in mast cell neoplasms: Recommendations of the European Competence Network on Mastocytosis","volume":"29","author":"Arock","year":"2015","journal-title":"Leukemia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"292","DOI":"10.2340\/00015555-2210","article-title":"Diagnosis of Mastocytosis in Children and Adults in Daily Clinical Practice","volume":"96","author":"Lange","year":"2016","journal-title":"Acta Derm. Venereol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.iac.2014.01.009","article-title":"Molecular defects in mastocytosis: KIT and beyond KIT","volume":"34","author":"Bibi","year":"2014","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.molimm.2014.03.013","article-title":"Molecular basis of mast cell disease","volume":"63","author":"Soucie","year":"2015","journal-title":"Mol. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1182\/blood.V98.3.880","article-title":"Association of the Q576R polymorphism in the interleukin-4 receptor alpha chain with indolent mastocytosis limited to the skin","volume":"98","author":"Daley","year":"2001","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/j.1398-9995.2008.01827.x","article-title":"Interleukin-13 promoter gene polymorphism -1112C\/T is associated with the systemic form of mastocytosis","volume":"64","author":"Nedoszytko","year":"2009","journal-title":"Allergy"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1111\/bjh.12086","article-title":"Comparative analysis of IL6 and IL6 receptor gene polymorphisms in mastocytosis","volume":"160","author":"Rausz","year":"2013","journal-title":"Br. J. Haematol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1159\/000489343","article-title":"The Possible Role of Gene Variant Coding Nonfunctional Toll-Like Receptor 2 in the Pathogenesis of Mastocytosis","volume":"177","author":"Nedoszytko","year":"2018","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"47","DOI":"10.2340\/00015555-2474","article-title":"Interleukin-31 Polymorphisms and Serum IL-31 Level in Patients with Mastocytosis: Correlation with Clinical Presen-tation and Pruritus","volume":"97","author":"Lange","year":"2017","journal-title":"Acta Derm. Venereol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/j.1365-2141.2007.06619.x","article-title":"Recent advances in the understanding of mastocytosis: The role of KIT mutations","volume":"138","author":"Orfao","year":"2007","journal-title":"Br. J. Haematol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1111\/j.1398-9995.2010.02477.x","article-title":"Gene expression profile, pathways, and transcriptional system regulation in indolent systemic mastocytosis","volume":"66","author":"Niedoszytko","year":"2011","journal-title":"Allergy"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Traina, F., Visconte, V., Jankowska, A.M., Makishima, H., O\u2019Keefe, C.L., Elson, P., Han, Y., Hsieh, F.H., Sekeres, M.A., and Mali, R.S. (2012). Single nucleotide polymorphism array lesions, TET2, DNMT3A, ASXL1 and CBL mutations are present in systemic mastocytosis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043090"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1182\/blood-2013-04-496448","article-title":"Comprehensive mutational profiling in advanced systemic mastocytosis","volume":"122","author":"Schwaab","year":"2013","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Damaj, G., Joris, M., Chandesris, O., Hanssens, K., Soucie, E., Canioni, D., Kolb, B., Durieu, I., Gyan, E., and Livideanu, C. (2014). ASXL1 but not TET2 mutations adversely impact overall survival of patients suffering systemic mastocytosis with associated clonal hematologic non-mast-cell diseases. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0085362"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1038\/leu.2015.4","article-title":"Molecular profiling of myeloid progenitor cells in multi-mutated advanced systemic mastocytosis identifies KIT D816V as a distinct and late event","volume":"29","author":"Jawhar","year":"2015","journal-title":"Leukemia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/leu.2015.284","article-title":"Additional mutations in SRSF2, ASXL1 and\/or RUNX1 identify a high-risk group of patients with KIT D816V(+) advanced systemic mastocytosis","volume":"30","author":"Jawhar","year":"2016","journal-title":"Leukemia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.bcp.2017.11.018","article-title":"ATP-binding Cassette transporter-2 (ABCA2) as a Therapeutic Target","volume":"151","author":"Davies","year":"2018","journal-title":"Biochem Pharmacol"},{"key":"ref_24","unstructured":"(2020, June 22). Reactome Pathways Database. Available online: https:\/\/reactome.org\/."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"68950","DOI":"10.18632\/oncotarget.10711","article-title":"Imatinib in systemic mastocytosis: A phase IV clinical trial in patients lacking exon 17 KIT mutations and review of the literature","volume":"8","author":"Matito","year":"2017","journal-title":"Oncotarget"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1016\/j.leukres.2011.05.006","article-title":"Tyrosine kinase inhibitors in the treatment of systemic mastocytosis","volume":"35","author":"Ustun","year":"2011","journal-title":"Leuk Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1080\/10428190400010775","article-title":"Mastocytosis: Pathology, genetics, and current options for therapy","volume":"46","author":"Valent","year":"2005","journal-title":"Leuk Lymphoma"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Berrondo, C., Flax, J., Kucherov, V., Siebert, A., Osinski, T., Rosenberg, A., Fucile, C., Richheimer, S., and Beckham, C.J. (2016). Expression of the Long Non-Coding RNA HOTAIR Correlates with Disease Progression in Bladder Cancer and Is Contained in Bladder Cancer Patient Urinary Exosomes. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0147236"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"46182","DOI":"10.1038\/srep46182","article-title":"Regulatory role of G9a and LSD1 in the Transcription of Olfactory Receptors during Leukaemia Cell Differentiation","volume":"7","author":"Jung","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e6","DOI":"10.5334\/ojb.22","article-title":"Biobank Lodz\u2014DNA Based Biobank at the University of Lodz, Poland","volume":"3","author":"Strapagiel","year":"2016","journal-title":"Open J. Bioresour."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"85","DOI":"10.31373\/ejtcm\/109495","article-title":"Biobank \u0141\u00f3d\u017a\u00ae\u2014Population based biobank at the University of \u0141\u00f3d\u017a, Poland","volume":"2","author":"Dobrowolska","year":"2019","journal-title":"Eur. J. Transl. Clin. Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Jarczak, J., Grochowalski, L., Marciniak, B., Lach, J., Slomka, M., Sobalska-Kwapis, M., Lorkiewicz, W., Pulaski, L., and Strapagiel, D. (2019). Mitochondrial DNA variability of the Polish population. Eur. J. Hum. Genet.","DOI":"10.1038\/s41431-019-0381-x"},{"key":"ref_33","unstructured":"Strapagiel, D., Slomka, M., John, S., and Gina, S. (2019). Method for Determination of Gender. (Patent 232652)."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1126\/science.273.5281.1516","article-title":"The future of genetic studies of complex human diseases","volume":"273","author":"Risch","year":"1996","journal-title":"Science"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/15\/5506\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:53:30Z","timestamp":1760176410000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/15\/5506"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,31]]},"references-count":34,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["ijms21155506"],"URL":"https:\/\/doi.org\/10.3390\/ijms21155506","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,31]]}}}