{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:48:02Z","timestamp":1762177682939,"version":"3.40.5"},"reference-count":56,"publisher":"Wiley","license":[{"start":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T00:00:00Z","timestamp":1709078400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genetics Research"],"published-print":{"date-parts":[[2024,2,28]]},"abstract":"<jats:p>Background and Objectives. Numerous genome-wide association studies have highlighted that chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder with an important genetic component. An important number of genes have been implicated in CLL etiology, with some of the most important being human leukocyte antigen (HLA) genes. The aim of this study was to analyze the association of CLL with certain HLA alleles in the Romanian population and to compare our results with previous findings. Materials and Methods. This study included 66 patients with CLL, diagnosed between 2020 and 2022, and 100 healthy controls. HLA class I and class II genes (HLA-A\/B\/C, HLA-DQA1\/DQB1\/DPA1\/DPB1, and HLA-DRB1\/3\/4\/5) were investigated using next-generation sequencing technology. Results. Several HLA alleles were strongly associated with CLL. The most important finding was that HLA-DRB1<jats:inline-formula><a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><a:msup><a:mrow\/><a:mi>\u2217<\/a:mi><\/a:msup><\/a:math><\/jats:inline-formula>04:02:01 (<jats:inline-formula><c:math xmlns:c=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><c:mi>p<\/c:mi><c:mo>=<\/c:mo><c:mn>0.001<\/c:mn><\/c:math><\/jats:inline-formula>, OR\u2009=\u20091.05) and HLA-DRB3<jats:inline-formula><e:math xmlns:e=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\"><e:msup><e:mrow\/><e:mi>\u2217<\/e:mi><\/e:msup><\/e:math><\/jats:inline-formula>02:01:01 (<jats:inline-formula><g:math xmlns:g=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\"><g:mi>p<\/g:mi><g:mo>=<\/g:mo><g:mn>0.009<\/g:mn><\/g:math><\/jats:inline-formula>, OR\u2009=\u20091.03) have a predisposing role in CLL development. Moreover, we identified that HLA-A<jats:inline-formula><i:math xmlns:i=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M5\"><i:msup><i:mrow\/><i:mi>\u2217<\/i:mi><\/i:msup><\/i:math><\/jats:inline-formula>24:02:01 0.01 (<jats:inline-formula><k:math xmlns:k=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M6\"><k:mi>p<\/k:mi><k:mo>=<\/k:mo><k:mn>0.01<\/k:mn><\/k:math><\/jats:inline-formula>, OR\u2009=\u20090.38), HLA-DQA1<jats:inline-formula><m:math xmlns:m=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M7\"><m:msup><m:mrow\/><m:mi>\u2217<\/m:mi><\/m:msup><\/m:math><\/jats:inline-formula>05:05:01 (<jats:inline-formula><o:math xmlns:o=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M8\"><o:mi>p<\/o:mi><o:mo>=<\/o:mo><o:mn>0.01<\/o:mn><\/o:math><\/jats:inline-formula>, OR\u2009=\u20090.56), HLA-DQB1<jats:inline-formula><q:math xmlns:q=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M9\"><q:msup><q:mrow\/><q:mi>\u2217<\/q:mi><\/q:msup><\/q:math><\/jats:inline-formula>03:02:01 (<jats:inline-formula><s:math xmlns:s=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M10\"><s:mi>p<\/s:mi><s:mo>=<\/s:mo><s:mn>0.03<\/s:mn><\/s:math><\/jats:inline-formula>, OR\u2009=\u20090.40), and HLA-DRB4<jats:inline-formula><u:math xmlns:u=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M11\"><u:msup><u:mrow\/><u:mi>\u2217<\/u:mi><\/u:msup><\/u:math><\/jats:inline-formula>01:03:01 (<jats:inline-formula><w:math xmlns:w=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M12\"><w:mi>p<\/w:mi><w:mo>=<\/w:mo><w:mn>0.03<\/w:mn><\/w:math><\/jats:inline-formula>, OR\u2009=\u20090.54 alleles have protective roles. Correlations between HLA expression and gender showed that women had a higher expression of protective HLA alleles when compared to men. Conclusions. Our data are the first to indicate that in Romanian patients with CLL, the HLA-A<jats:inline-formula><y:math xmlns:y=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M13\"><y:msup><y:mrow\/><y:mi>\u2217<\/y:mi><\/y:msup><\/y:math><\/jats:inline-formula>24:02:01 and HLA-DQA1<jats:inline-formula><ab:math xmlns:ab=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M14\"><ab:msup><ab:mrow\/><ab:mi>\u2217<\/ab:mi><\/ab:msup><\/ab:math><\/jats:inline-formula>05:05:01 alleles have a protective role against CLL development, whereas HLA-DRB1<jats:inline-formula><cb:math xmlns:cb=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M15\"><cb:msup><cb:mrow\/><cb:mi>\u2217<\/cb:mi><\/cb:msup><\/cb:math><\/jats:inline-formula>04:02:01 and HLA-DRB3<jats:inline-formula><eb:math xmlns:eb=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M16\"><eb:msup><eb:mrow\/><eb:mi>\u2217<\/eb:mi><\/eb:msup><\/eb:math><\/jats:inline-formula>02:01:01alleles are positively associated with CLL.<\/jats:p>","DOI":"10.1155\/2024\/8852876","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T14:05:10Z","timestamp":1709129110000},"page":"1-9","source":"Crossref","is-referenced-by-count":2,"title":["HLA Gene Polymorphisms in Romanian Patients with Chronic Lymphocytic Leukemia"],"prefix":"10.1155","volume":"2024","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5202-4657","authenticated-orcid":true,"given":"Maria","family":"Tizu","sequence":"first","affiliation":[{"name":"Immunology and Transplant Immunology, Carol Davila University of Medicine and Pharmacy, 258 Fundeni Avenue, Bucharest 022328, Romania"},{"name":"Centre of Immunogenetics and Virology, Fundeni Clinical Institute, 258 Fundeni Avenue, Bucharest 022328, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7565-9964","authenticated-orcid":true,"given":"Bogdan","family":"Calenic","sequence":"additional","affiliation":[{"name":"Immunology and Transplant Immunology, Carol Davila University of Medicine and Pharmacy, 258 Fundeni Avenue, Bucharest 022328, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihai","family":"H\u00e2rza","sequence":"additional","affiliation":[{"name":"Immunology and Transplant Immunology, Carol Davila University of Medicine and Pharmacy, 258 Fundeni Avenue, Bucharest 022328, Romania"},{"name":"Centre of Immunogenetics and Virology, Fundeni Clinical Institute, 258 Fundeni Avenue, Bucharest 022328, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3839-2199","authenticated-orcid":true,"given":"Bogdan M.","family":"Cristea","sequence":"additional","affiliation":[{"name":"Immunology and Transplant Immunology, Carol Davila University of Medicine and Pharmacy, 258 Fundeni Avenue, Bucharest 022328, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4284-8654","authenticated-orcid":true,"given":"Ion","family":"Maruntelu","sequence":"additional","affiliation":[{"name":"Centre of Immunogenetics and Virology, Fundeni Clinical Institute, 258 Fundeni Avenue, Bucharest 022328, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9290-5533","authenticated-orcid":true,"given":"Andreea M.","family":"Caragea","sequence":"additional","affiliation":[{"name":"Immunology and Transplant Immunology, Carol Davila University of Medicine and Pharmacy, 258 Fundeni Avenue, Bucharest 022328, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9721-5915","authenticated-orcid":true,"given":"Adriana","family":"Talangescu","sequence":"additional","affiliation":[{"name":"Centre of Immunogenetics and Virology, Fundeni Clinical Institute, 258 Fundeni Avenue, Bucharest 022328, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8743-3236","authenticated-orcid":true,"given":"Alina","family":"Dima","sequence":"additional","affiliation":[{"name":"Colentina Clinical Hospital, Rheumatology Department Bucharest, 19-21 Stefan Cel Mare Street, Bucharest 020125, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra E.","family":"Constantinescu","sequence":"additional","affiliation":[{"name":"Immunology and Transplant Immunology, Carol Davila University of Medicine and Pharmacy, 258 Fundeni Avenue, Bucharest 022328, 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