{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T18:10:59Z","timestamp":1789236659309,"version":"build-2803163510"},"reference-count":47,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T00:00:00Z","timestamp":1719360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Hygiene and Epidemiology, Pomeranian Medical University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The aim of the present study was to analyze the association of the TLR2 (Toll-like receptor 2 gene) 2258G&gt;A (rs5743708), TLR4 (Toll-like receptor 4 gene) 896A&gt;G (rs4986790), and TLR4 1196C&gt;T (rs4986791) polymorphisms with dental caries in Polish children. The participants, 261 15-year-old children, were divided into two groups: 82 cases (i.e., children with DMFT (Decayed, Missing, and Filled Teeth) index &gt;5, having either moderate or high caries experience, assigned as the \u201chigher\u201d caries experience group) and 179 controls (i.e., children with DMFT \u2264 5, having either low or very low caries experience, assigned as the \u201clower\u201d caries experience group). Genomic DNA was isolated from buccal swabs, and genotyping was determined by means of real-time PCR (polymerase chain reaction). There were no significant differences in the genotype or allele distributions in all tested SNPs (single nucleotide polymorphisms) between children with \u201chigher\u201d caries experience and those with \u201clower\u201d caries experience. TLR4 haplotype frequencies did not differ significantly between cases and controls. In an additional analysis with another case definition applied (subjects with DMFT \u2265 1 were assigned as \u201ccases\u201d, whereas children with DMFT = 0 were assigned as \u201ccontrols\u201d), no significant differences in the TLR2 and TLR4 genotype, allele frequencies, and TLR4 haplotype frequencies were found between the case and the control groups. The results of the present study broaden our knowledge on the potential genetic factors that might affect caries risk and suggest that TLR2 rs5743708 and TLR4 rs4986790 and rs4986791 SNPs are not associated with dental caries susceptibility in Polish children.<\/jats:p>","DOI":"10.3390\/ijms25136985","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T05:11:39Z","timestamp":1719465099000},"page":"6985","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["TLR2 and TLR4 Polymorphisms Are Not Associated with Dental Caries in Polish Children"],"prefix":"10.3390","volume":"25","author":[{"given":"Marta","family":"Milona","sequence":"first","affiliation":[{"name":"Department of Hygiene and Epidemiology, Pomeranian Medical University in Szczecin, Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2874-985X","authenticated-orcid":false,"given":"Tomasz","family":"Olszowski","sequence":"additional","affiliation":[{"name":"Department of Hygiene and Epidemiology, Pomeranian Medical University in Szczecin, Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0159-5803","authenticated-orcid":false,"given":"Izabela","family":"Uzar","sequence":"additional","affiliation":[{"name":"Department of General Pharmacology and Pharmacoeconomics, Pomeranian Medical University in Szczecin, \u017bo\u0142nierska 48, 71-210 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9415-2758","authenticated-orcid":false,"given":"Krzysztof","family":"Safranow","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4374-2568","authenticated-orcid":false,"given":"Joanna","family":"Janiszewska-Olszowska","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Dentistry, Pomeranian Medical University in Szczecin, Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1096-9993","authenticated-orcid":false,"given":"Monika","family":"Szmidt-K\u0105dys","sequence":"additional","affiliation":[{"name":"Department of Conservative Dentistry with Endodontics, Pomeranian Medical University in Szczecin, Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6395-7670","authenticated-orcid":false,"given":"Hubert","family":"Rola","sequence":"additional","affiliation":[{"name":"MIL-MED Healthcare Center, Ruta 8, 72-300 Gryfice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3348-1950","authenticated-orcid":false,"given":"Maciej","family":"Sikora","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"},{"name":"Department of Maxillofacial Surgery, Hospital of the Ministry of Interior, Wojska Polskiego 51, 25-375 Kielce, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4497-4395","authenticated-orcid":false,"given":"Dariusz","family":"Chlubek","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gra\u017cyna","family":"Adler","sequence":"additional","affiliation":[{"name":"Department of Studies in Anthropogenetics and Biogerontology, Pomeranian Medical University in Szczecin, \u017bo\u0142nierska 48, 71-210 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,26]]},"reference":[{"key":"ref_1","unstructured":"Institute for Health Metrics and Evaluation (IHME) (2020). Global Burden of Disease Collaborative Network. Global Burden of Disease Study 2019 (GBD 2019), Institute for Health Metrics and Evaluation (IHME)."},{"key":"ref_2","unstructured":"World Health Organization (2022). Global Oral Health Status Report: Towards Universal Health Coverage for Oral Health by 2030, World Health Organization."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/s41415-021-3775-4","article-title":"Understanding dental caries as a non-communicable disease","volume":"231","author":"Pitts","year":"2021","journal-title":"Br. Dent. J."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zou, T., Foxman, B., McNeil, D.W., Weinberg, S.M., Marazita, M.L., and Shaffer, J.R. (2023). Genome-Wide Analysis of Dental Caries Variability Reveals Genotype-by-Environment Interactions. Genes, 14.","DOI":"10.3390\/genes14030736"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1159\/000369103","article-title":"Genetic susceptibility to dental caries differs between the sexes: A family-based study","volume":"49","author":"Shaffer","year":"2015","journal-title":"Caries Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1159\/000314676","article-title":"Genes and their effects on dental caries may differ between primary and permanent dentitions","volume":"44","author":"Wang","year":"2010","journal-title":"Caries Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1111\/odi.13806","article-title":"FCN1 polymorphisms are not the markers of dental caries susceptibility in Polish children: A case-control study","volume":"28","author":"Olszowski","year":"2022","journal-title":"Oral Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1111\/j.1601-0825.2011.01887.x","article-title":"MBL2, MASP2, AMELX, and ENAM gene polymorphisms and dental caries in Polish children","volume":"18","author":"Olszowski","year":"2012","journal-title":"Oral Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1159\/000455054","article-title":"The Lack of Association between FCN2 Gene Promoter Region Polymorphisms and Dental Caries in Polish Children","volume":"51","author":"Olszowski","year":"2017","journal-title":"Caries Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"230251","DOI":"10.1155\/2015\/230251","article-title":"Dental Pulp Defence and Repair Mechanisms in Dental Caries","volume":"2015","author":"Farges","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e12771","DOI":"10.1111\/sji.12771","article-title":"Toll-like receptor polymorphism in host immune response to infectious diseases: A review","volume":"90","author":"Mukherjee","year":"2019","journal-title":"Scand J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Oliveira-Nascimento, L., Massari, P., and Wetzler, L.M. (2012). The Role of TLR2 in Infection and Immunity. Front. Immunol., 3.","DOI":"10.3389\/fimmu.2012.00079"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/j.1399-302X.2007.00310.x","article-title":"Differential regulation of immune responses by odontoblasts","volume":"22","author":"Veerayutthwilai","year":"2007","journal-title":"Oral Microbiol. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1016\/j.joen.2007.05.018","article-title":"Expression of toll-like receptor 2 and 4 in dental pulp","volume":"33","author":"Mutoh","year":"2007","journal-title":"J. Endod."},{"key":"ref_15","first-page":"210","article-title":"Correlation between salivary Toll like receptor-2 concentration and early childhood caries","volume":"11","author":"Malekafzali","year":"2014","journal-title":"Iran J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Zhao, A., Blackburn, C., Chin, J., and Srinivasan, M. (2014). Soluble toll like receptor 2 (TLR-2) is increased in saliva of children with dental caries. BMC Oral Health, 14.","DOI":"10.1186\/1472-6831-14-108"},{"key":"ref_17","first-page":"4488","article-title":"Activation of autophagy in pulpitis is associated with TLR4","volume":"10","author":"He","year":"2017","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.medin.2013.08.006","article-title":"TLR2-TLR4\/CD14 polymorphisms and predisposition to severe invasive infections by Neisseria meningitidis and Streptococcus pneumoniae","volume":"38","author":"Varillas","year":"2014","journal-title":"Med. Intensiv."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1177\/1753425919862354","article-title":"Associations between genetic polymorphisms of TLRs and susceptibility to tuberculosis: A meta-analysis","volume":"26","author":"Zhou","year":"2020","journal-title":"Innate Immun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"38947","DOI":"10.1038\/srep38947","article-title":"The relationship between toll like receptor 4 gene rs4986790 and rs4986791 polymorphisms and sepsis susceptibility: A meta-analysis","volume":"6","author":"Liu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ijid.2017.04.024","article-title":"Analysis of TLR2, TLR4, and TLR9 single nucleotide polymorphisms in children with bacterial meningitis and their healthy family members","volume":"60","author":"Gowin","year":"2017","journal-title":"Int. J. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Kim, Y.C., and Jeong, B.H. (2020). Strong Association of the rs4986790 Single Nucleotide Polymorphism (SNP) of the Toll-Like Receptor 4 (TLR4) Gene with Human Immunodeficiency Virus (HIV) Infection: A Meta-Analysis. Genes, 12.","DOI":"10.3390\/genes12010036"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ijid.2014.04.001","article-title":"Relationship between toll-like receptor 2 Arg677Trp and Arg753Gln and toll-like receptor 4 Asp299Gly polymorphisms and cytomegalovirus infection","volume":"25","author":"Paradowska","year":"2014","journal-title":"Int. J. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e7828","DOI":"10.7717\/peerj.7828","article-title":"TLR4 polymorphisms may increase susceptibility to periodontitis in Pg-positive individuals","volume":"7","author":"Li","year":"2019","journal-title":"PeerJ"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4029217","DOI":"10.1155\/2019\/4029217","article-title":"The Influence of TLR4, CD14, OPG, and RANKL Polymorphisms in Periodontitis: A Case-Control Study","volume":"2019","author":"Zacarias","year":"2019","journal-title":"Mediat. Inflamm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1007\/s00795-020-00263-5","article-title":"Variants in taste genes on caries risk and caries activity status","volume":"53","author":"Saydam","year":"2020","journal-title":"Med. Mol. Morphol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1038\/sj.gene.6364282","article-title":"Gingival epithelial cells heterozygous for Toll-like receptor 4 polymorphisms Asp299Gly and Thr399ile are hypo-responsive to Porphyromonas gingivalis","volume":"7","author":"Kinane","year":"2006","journal-title":"Genes Immun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"154284","DOI":"10.1016\/j.prp.2022.154284","article-title":"Polymorphisms and haplotypes of TLR-4\/9 associated with bacterial infection, gingival inflammation\/recession and oral cancer","volume":"241","author":"Jha","year":"2023","journal-title":"Pathol. Res. Pract."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"13154","DOI":"10.1038\/s41598-020-70129-4","article-title":"TLR4 896A\/G and TLR9 1174G\/A polymorphisms are associated with the risk of infectious mononucleosis","volume":"10","author":"Szenborn","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1586762","DOI":"10.1155\/2018\/1586762","article-title":"SNP Analysis of Caries and Initial Caries in Finnish Adolescents","volume":"2018","author":"Raivisto","year":"2018","journal-title":"Int. J. Dent."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Wang, Q., Jia, P., Cuenco, K.T., Feingold, E., Marazita, M.L., Wang, L., and Zhao, Z. (2013). Multi-dimensional prioritization of dental caries candidate genes and its enriched dense network modules. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076666"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1016\/j.recesp.2011.02.024","article-title":"Toll-like receptor 2 R753Q polymorphisms are associated with an increased risk of infective endocarditis","volume":"64","author":"Bustamante","year":"2011","journal-title":"Rev. Esp. Cardiol."},{"key":"ref_33","first-page":"91","article-title":"Toll-like receptor cascade and gene polymorphism in host-pathogen interaction in Lyme disease","volume":"9","author":"Rahman","year":"2016","journal-title":"J. Inflamm. Res."},{"key":"ref_34","first-page":"404","article-title":"The role of toll-like receptors (TLRs) in urinary tract infections (UTIs)","volume":"69","author":"Behzadi","year":"2016","journal-title":"Cent. Eur. J. Urol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.molimm.2013.10.004","article-title":"Lipoteichoic acid of Streptococcus mutans interacts with Toll-like receptor 2 through the lipid moiety for induction of inflammatory mediators in murine macrophages","volume":"57","author":"Hong","year":"2014","journal-title":"Mol. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1111\/j.1600-051X.2011.01702.x","article-title":"Stimulants of Toll-like receptors 2 and 4 are elevated in saliva of periodontitis patients compared with healthy subjects","volume":"38","author":"Lappin","year":"2011","journal-title":"J. Clin. Periodontol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1016\/j.joen.2014.03.015","article-title":"TLR4 activation by lipopolysaccharide and Streptococcus mutans induces differential regulation of proliferation and migration in human dental pulp stem cells","volume":"40","author":"Liu","year":"2014","journal-title":"J. Endod."},{"key":"ref_38","first-page":"153","article-title":"Locations of TLR4 in healthy dental pulp tissue and dental pulp tissue affected by deep caries","volume":"25","author":"Liu","year":"2017","journal-title":"J. Prev. Treat. Stomatol. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e1268","DOI":"10.1002\/mgg3.1268","article-title":"Human closed and open apex premolar teeth express different toll-like receptor","volume":"8","author":"Jafari","year":"2020","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jdsr.2018.03.001","article-title":"The roles of odontoblasts in dental pulp innate immunity","volume":"54","author":"Yumoto","year":"2018","journal-title":"Jpn. Dent. Sci. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"53","DOI":"10.3844\/ajavsp.2017.53.57","article-title":"Immunologic Aspect of Mice (Mus musculus) Dental Caries Induced by Streptococcus mutans","volume":"12","author":"Murwani","year":"2017","journal-title":"Am. J. Anim. Vet. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Alotaibi, R.N., Howe, B.J., Chernus, J.M., Mukhopadhyay, N., Sanchez, C., Deleyiannis, F.W.B., Neiswanger, K., Padilla, C., Poletta, F.A., and Orioli, I.M. (2021). Genome-Wide Association Study (GWAS) of dental caries in diverse populations. BMC Oral Health, 21.","DOI":"10.1186\/s12903-021-01670-5"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2773","DOI":"10.1038\/s41467-019-10630-1","article-title":"Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data","volume":"10","author":"Shungin","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1007\/s12026-015-8640-6","article-title":"Association of TLR1, TLR2, TLR4, TLR6, and TIRAP polymorphisms with disease susceptibility","volume":"62","author":"Noreen","year":"2015","journal-title":"Immunol Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1159\/000261572","article-title":"Comparison of different methods for the diagnosis of fissure caries without cavitation","volume":"27","author":"Lussi","year":"1993","journal-title":"Caries Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"C56","DOI":"10.1177\/154405910408301s12","article-title":"Visual and visuo-tactile detection of dental caries","volume":"83","author":"Ismail","year":"2004","journal-title":"J. Dent. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1177\/154405910808700506","article-title":"Genome-wide scan finds suggestive caries loci","volume":"87","author":"Vieira","year":"2008","journal-title":"J. Dent. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/6985\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:04:49Z","timestamp":1760108689000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/6985"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,26]]},"references-count":47,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["ijms25136985"],"URL":"https:\/\/doi.org\/10.3390\/ijms25136985","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,26]]}}}