{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:36:24Z","timestamp":1791311784370,"version":"4.3.1"},"reference-count":109,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T00:00:00Z","timestamp":1684713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King Edward Medical University","award":["22242\/KEMU\/2016"],"award-info":[{"award-number":["22242\/KEMU\/2016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Recurrent aphthous stomatitis (RAS) is a benign ulcerative condition, defined by the recurrent formation of non-contagious mucosal ulcers. Surfactant protein D (SP-D) is secreted frequently at surfaces exposed directly to body fluids. This study aims to investigate the association of SP-D single nucleotide polymorphisms (SNPs) with the onset of RAS. Blood samples from 212 subjects (106 cases\/controls each) were collected during 2019 and genotyped for SP-D SNPs (rs721917, rs2243639, rs3088308) by polymerase chain reaction and restriction fragment length polymorphism followed by 12% polyacrylamide gel electrophoresis. Minor aphthous (75.5%) was the commonly observed ulcer type as compared to herpetiform (21.7%) and major aphthous ulcers (2.8%). A family history of RAS was reported in 70% of cases. RAS was found significantly associated with rs3088308 genotypes T\/A (95% (Cl): 1.57\u20135.03, p = 0.0005), A\/A (95% (Cl): 1.8\u20136.7, p = 0.0002), T-allele (95% (Cl): 1.09\u20132.36, p = 0.01), A-allele (95% (Cl): 1.42\u20133.91, p = 0.01), rs721917 genotype T\/T (95% (Cl): 1.15\u201325.35, p = 0.03), and T-allele (95% (Cl): 1.28\u20133.10, p = 0.002). Female gender and obese body mass index (BMI) were significantly associated with rs3088308 genotypes T\/A (95% (CI): 1.89\u201315.7, p = 0.001), T\/T (95% (Cl): 1.52\u201311.9, p = 0.005), A-allele (95% (Cl): 1.65\u20137.58, p &lt; 0.001), and T-allele (95% (Cl): 1.4\u201310.1, p &lt;0.001) and rs721917 genotype T\/T (95% (CI) = 1.3\u201333, p = 0.02), respectively. This study describes the association of SP-D SNPs (rs721917, rs3088308) with RAS in the Pakistani population.<\/jats:p>","DOI":"10.3390\/genes14051119","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T02:28:42Z","timestamp":1684722522000},"page":"1119","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Association of Surfactant Protein D Single Nucleotide Polymorphisms rs721917, rs2243639, rs3088308 with Recurrent Aphthous Stomatitis in Pakistani Population"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7052-7786","authenticated-orcid":false,"given":"Zainab","family":"Rizvi","sequence":"first","affiliation":[{"name":"Department of Oral Pathology, de\u2019 Montmorency College of Dentistry, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nakhshab","family":"Choudhry","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, King Edward Medical University, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4379-0578","authenticated-orcid":false,"given":"Aamir Jamal","family":"Gondal","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, King Edward Medical University, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3783-6093","authenticated-orcid":false,"given":"Nighat","family":"Yasmin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, King Edward Medical University, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e7278925","DOI":"10.1155\/2016\/7278925","article-title":"Diagnostic features of common oral ulcerative lesions: An updated decision tree","volume":"2016","author":"Mortazavi","year":"2016","journal-title":"Int. J. Dent."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s11136-011-9925-4","article-title":"Impacts of recurrent aphthous stomatitis on quality of life of 12-and 15-year-old Thai children","volume":"21","author":"Krisdapong","year":"2012","journal-title":"Qual. Life Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"564","DOI":"10.12968\/denu.2015.42.6.564","article-title":"Management of recurrent aphthous stomatitis in children","volume":"42","author":"Wallace","year":"2015","journal-title":"Dent. Update"},{"key":"ref_4","first-page":"26","article-title":"Recurrent aphthous stomatitis: A review","volume":"10","author":"Edgar","year":"2017","journal-title":"J. Clin. Aesthet. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"337","DOI":"10.12968\/hmed.2015.76.6.337","article-title":"A guide to oral ulceration for the medical physician","volume":"76","author":"Goel","year":"2015","journal-title":"Br. J. Hosp. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"463","DOI":"10.47102\/annals-acadmedsg.V41N10p463","article-title":"Oral aphthosis: Management gaps and recent advances","volume":"41","author":"Liang","year":"2012","journal-title":"Ann. Acad. Med. Singap."},{"key":"ref_7","first-page":"47","article-title":"Essentials of recurrent aphthous stomatitis","volume":"11","author":"Rivera","year":"2019","journal-title":"Biomed. Rep."},{"key":"ref_8","first-page":"6218","article-title":"Risk factors of recurrent aphthous ulceration among university students","volume":"8","author":"Shi","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_9","first-page":"202","article-title":"Recurrent aphthous ulcers\u2014Still a challenging clinical entity","volume":"14","author":"Swain","year":"2017","journal-title":"Apollo Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"15","DOI":"10.2334\/josnusd.42.15","article-title":"Oral recurrent aphthous ulcers\/stomatitis: Prevalence in Malaysia and an epidemiological update","volume":"42","author":"Zain","year":"2000","journal-title":"J. Oral Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/0030-4220(72)90470-7","article-title":"Aphthous lesions","volume":"33","author":"Stanley","year":"1972","journal-title":"Oral Surg. Oral Med. Oral Path."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"252","DOI":"10.4103\/0973-029X.86669","article-title":"Recurrent aphthous stomatitis","volume":"15","author":"Preeti","year":"2011","journal-title":"J. Oral Maxillofac. Path."},{"key":"ref_13","first-page":"281","article-title":"Recurrent aphthous stomatitis","volume":"58","author":"Akintoye","year":"2014","journal-title":"Dent. Clin."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s00005-013-0261-y","article-title":"Etiopathogenesis of recurrent aphthous stomatitis and the role of immunologic aspects: Literature review","volume":"62","author":"Szponar","year":"2014","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1046\/j.1365-2036.2003.01782.x","article-title":"Oral ulceration\u2013aetiopathogenesis, clinical diagnosis and management in the gastrointestinal clinic","volume":"18","author":"Field","year":"2003","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_16","first-page":"113","article-title":"Pathogenesis of recurrent aphthous stomatitis: A review of literature","volume":"20","author":"Khan","year":"2006","journal-title":"Proc. Shaikh Zayed Postgrad. Med. Inst."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e21694","DOI":"10.5812\/ircmj.21694","article-title":"The most common herbs to cure the most common oral disease: Stomatitis recurrent aphthous ulcer (RAU)","volume":"18","author":"Hamedi","year":"2016","journal-title":"Iran. Red Crescent Med. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/prd.12262","article-title":"Recurrent oral ulceration: Etiology, classification, management, and diagnostic algorithm","volume":"80","author":"Bilodeau","year":"2019","journal-title":"Periodontology 2000"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11","DOI":"10.5770\/cgj.18.123","article-title":"Prevalence and distribution of oral mucosal lesions in a geriatric Indian population","volume":"18","author":"Patil","year":"2015","journal-title":"Can. Geriatr. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1111\/jop.12264","article-title":"Prevalence and distribution of oral mucosal lesions: A cross-sectional study in Shanghai, China","volume":"44","author":"Feng","year":"2015","journal-title":"J. Oral Pathol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Safadi, R.A. (2009). Prevalence of recurrent aphthous ulceration in Jordanian dental patients. BMC Oral Health, 9.","DOI":"10.1186\/1472-6831-9-31"},{"key":"ref_22","first-page":"207","article-title":"The prevalence of oral aphthosis in a normal population in Iran: A WHO-ILAR COPCORD study","volume":"11","author":"Davatchi","year":"2008","journal-title":"Arch. Iran Med."},{"key":"ref_23","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":"Souza","year":"2017","journal-title":"An. Bras. Dermatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1111\/j.1600-0714.2004.00241.x","article-title":"An exploration of point, annual, and lifetime prevalence in characterizing recurrent aphthous stomatitis in USA children and youths","volume":"33","author":"Shulman","year":"2004","journal-title":"J. Oral Path. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e89","DOI":"10.4317\/jced.51042","article-title":"Prevalence of recurrent aphthous ulceration experience in patients attending Piramird dental speciality in Sulaimani City","volume":"5","author":"Abdullah","year":"2013","journal-title":"J. Clin. Exp. Dent."},{"key":"ref_26","first-page":"419","article-title":"Frequency Of Apthous Ulcers\u2014A Study","volume":"37","author":"Lakdawala","year":"2017","journal-title":"Pak. Oral Dent. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1111\/odi.13490","article-title":"A family-based genome-wide association study of recurrent aphthous stomatitis","volume":"26","author":"Bankvall","year":"2020","journal-title":"Oral Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s12969-021-00552-y","article-title":"Genetic and immunologic findings in children with recurrent aphthous stomatitis with systemic inflammation","volume":"19","author":"Girardelli","year":"2021","journal-title":"Pediatr. Rheumatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"405","DOI":"10.3109\/08820139.2014.880119","article-title":"Interleukin-10 gene polymorphisms in recurrent aphthous stomatitis","volume":"43","author":"Najafi","year":"2014","journal-title":"Immunol. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.archoralbio.2006.08.008","article-title":"Investigation of functional gene polymorphisms IL-1\u03b2, IL-6, IL-10 and TNF-\u03b1 in individuals with recurrent aphthous stomatitis","volume":"52","author":"Diniz","year":"2007","journal-title":"Arch. Oral Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s00403-013-1406-x","article-title":"Effects of interleukin (IL)-6 gene polymorphisms on recurrent aphthous stomatitis","volume":"306","author":"Karakus","year":"2014","journal-title":"Arch. Dermatol. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1111\/odi.12190","article-title":"Association of MMP but not TIMP-1 gene polymorphisms with recurrent aphthous stomatitis","volume":"20","author":"Karasneh","year":"2014","journal-title":"Oral Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/j.1399-0039.2008.01056.x","article-title":"Increased plasma concentration of surfactant protein D in chronic periodontitis independent of SFTPD genotype: Potential role as a biomarker","volume":"72","author":"Glas","year":"2008","journal-title":"Tissue Antigens"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1369\/0022155418766063","article-title":"Immunolocalization of surfactant proteins SP-A, SP-B, SP-C, and SP-D in infantile labial glands and mucosa","volume":"66","author":"Stoeckelhuber","year":"2018","journal-title":"J. Histochem. Cytochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/j.1939-1676.2008.0269.x","article-title":"Role of lung surfactant in respiratory disease: Current knowledge in large animal medicine","volume":"23","author":"Christmann","year":"2009","journal-title":"J. Vet. Intern. Med."},{"key":"ref_36","first-page":"131","article-title":"An insight into the diverse roles of surfactant proteins, SP-A and SP-D in innate and adaptive immunity","volume":"7","author":"Nayak","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5866","DOI":"10.4049\/jimmunol.164.11.5866","article-title":"Localization of lung surfactant protein D on mucosal surfaces in human tissues","volume":"164","author":"Madsen","year":"2000","journal-title":"J. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s00418-009-0609-x","article-title":"Human parotid and submandibular glands express and secrete surfactant proteins A, B, C and D","volume":"132","author":"Beileke","year":"2009","journal-title":"Histochem. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1155\/2012\/802145","article-title":"SP-D polymorphisms and the risk of COPD","volume":"33","author":"Shakoori","year":"2012","journal-title":"Dis. Markers"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.aanat.2017.03.002","article-title":"Structure, genetics and function of the pulmonary associated surfactant proteins A and D: The extra-pulmonary role of these C type lectins","volume":"211","author":"Vieira","year":"2017","journal-title":"Ann. Anat."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3389\/fmed.2018.00018","article-title":"Surfactant protein D in respiratory and non-respiratory diseases","volume":"5","author":"Sorensen","year":"2018","journal-title":"Front.Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00251-005-0775-5","article-title":"Polymorphisms in the human surfactant protein-D (SFTPD) gene: Strong evidence that serum levels of surfactant protein-D (SP-D) are genetically influenced","volume":"57","author":"Heidinger","year":"2005","journal-title":"Immunogenetics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.4049\/jimmunol.174.3.1532","article-title":"A common polymorphism in the SFTPD gene influences assembly, function, and concentration of surfactant protein D","volume":"174","author":"Garred","year":"2005","journal-title":"J. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"L1010","DOI":"10.1152\/ajplung.00487.2005","article-title":"Genetic and environmental influences of surfactant protein D serum levels","volume":"290","author":"Hjelmborg","year":"2006","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.ajhg.2008.11.010","article-title":"Genetic defects in surfactant protein A2 are associated with pulmonary fibrosis and lung cancer","volume":"84","author":"Wang","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"538","DOI":"10.2500\/ajr.2007.21.3070","article-title":"Innate and adaptive mediators in cystic fibrosis and allergic fungal rhinosinusitis","volume":"21","author":"Skinner","year":"2007","journal-title":"Am. J. Rhinol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1097\/PCC.0b013e3181ae5a4c","article-title":"Surfactant phospholipids, surfactant proteins, and inflammatory markers during acute lung injury in children","volume":"11","author":"Todd","year":"2010","journal-title":"Pediatr. Crit. Care Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1053\/j.semperi.2006.09.002","article-title":"Surfactant protein polymorphisms and neonatal lung disease","volume":"30","author":"Hallman","year":"2006","journal-title":"Semin. Perinatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1111\/j.1651-2227.2007.00319.x","article-title":"Haplotypes of the surfactant protein genes A and D as susceptibility factors for the development of respiratory distress syndrome","volume":"96","author":"Thomas","year":"2007","journal-title":"Acta Paediatr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5125","DOI":"10.1021\/pr800423x","article-title":"Proteomics of human lung tissue identifies surfactant protein A as a marker of chronic obstructive pulmonary disease","volume":"7","author":"Ohlmeier","year":"2008","journal-title":"J. Proteome Res."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Puthothu, B., Forster, J., Heinze, J., Heinzmann, A., and Krueger, M. (2007). Surfactant protein B polymorphisms are associated with severe respiratory syncytial virus infection, but not with asthma. BMC Pulm. Med., 7.","DOI":"10.1186\/1471-2466-7-6"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1159\/000272047","article-title":"Pulmonary surfactant: An immunological perspective","volume":"25","author":"Chroneos","year":"2010","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.atherosclerosis.2015.12.037","article-title":"Association between surfactant protein D (SFTPD) gene and subclinical carotid artery atherosclerosis","volume":"246","author":"Sorensen","year":"2016","journal-title":"Atherosclerosis"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Xu, J., Chen, Y., Tang, L., Teng, X., Feng, L., Jin, L., Wang, G., and Wang, L. (2022). Association of surfactant protein D gene polymorphism with susceptibility to gestational diabetes mellitus: A case\u2013control study. BMC Pregnancy Childbirth, 22.","DOI":"10.1186\/s12884-022-04541-1"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3000605211017724","DOI":"10.1177\/03000605211017724","article-title":"Relationship between dietary factors and recurrent aphthous stomatitis in China: A cross-sectional study","volume":"49","author":"Xu","year":"2021","journal-title":"J. Int. Med. Res."},{"key":"ref_56","first-page":"1823","article-title":"Association of Body Mass Index with Lifestyle Behaviours among Students of Punjab University","volume":"9","author":"Shahzad","year":"2020","journal-title":"Int. J. Med. Dent. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/j.1399-3038.2005.00353.x","article-title":"Amino acid variants in Surfactant protein D are not associated with bronchial asthma","volume":"17","author":"Krueger","year":"2006","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1007\/s00296-009-1036-y","article-title":"Familial Beh\u00e7et\u2019s disease","volume":"30","author":"Yilmaz","year":"2010","journal-title":"Rheumatol. Int."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1111\/odi.12131","article-title":"Elevated serum IgE in recurrent aphthous stomatitis and associations with disease characteristics","volume":"20","author":"Almoznino","year":"2014","journal-title":"Oral Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1177\/154411130401500405","article-title":"Adverse drug reactions in the orofacial region","volume":"15","author":"Scully","year":"2004","journal-title":"Crit. Rev. Oral Biol. Med."},{"key":"ref_61","first-page":"124","article-title":"Haematological parameters and recurrent aphthous stomatitis","volume":"23","author":"Khan","year":"2013","journal-title":"J. Coll. Physicians Surg. Pak."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"215","DOI":"10.25301\/JPDA.303.215","article-title":"Awareness Regarding Oral Aphthous Ulcers and its Risk Factors Among BDS and MBBS Students-A Cross-Sectional Survey","volume":"30","author":"Azfar","year":"2021","journal-title":"J. Pak. Dent. Assoc."},{"key":"ref_63","first-page":"95","article-title":"Recurrent Aphthout Stomatitis","volume":"31","author":"Ship","year":"2000","journal-title":"Quintessence Int."},{"key":"ref_64","first-page":"80","article-title":"Prevalence of recurrent aphthous ulcers in dental student: A questionnaire based study","volume":"180","author":"Rathod","year":"2017","journal-title":"Stress"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1111\/eos.12577","article-title":"Recurrent aphthous stomatitis and gene variability in selected interleukins: A case\u2013control study","volume":"126","author":"Linhartova","year":"2018","journal-title":"Eur. J. Oral Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.annder.2018.07.009","article-title":"Aphthous mouth ulcers as an initial manifestation of s\u00e9cukinumab-induced inflammatory bowel disease","volume":"145","author":"Grimaux","year":"2018","journal-title":"Ann. Dermatol. Venereol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e24","DOI":"10.1016\/j.adaj.2018.09.011","article-title":"Patients who seek professional treatment of recurrent aphthous stomatitis probably have an increased risk of having head and neck cancer and other types of cancers","volume":"150","year":"2019","journal-title":"J. Am. Dent. Assoc."},{"key":"ref_68","first-page":"116","article-title":"Incidence of Aphthous Ulcers in All Forms of Tobacco Users, Mixed Habits and Non-Users","volume":"15","author":"Masood","year":"2020","journal-title":"J. Islam. Int. Med. Coll."},{"key":"ref_69","first-page":"9","article-title":"Pattern of presentation of oral ulcerations in patients attending an oral medicine clinic in Nigeria","volume":"16","author":"Oyetola","year":"2018","journal-title":"Ann. Ib. Postgrad. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1590\/abd1806-4841.20186228","article-title":"Recurrent aphthous ulceration: An epidemiological study of etiological factors, treatment and differential diagnosis","volume":"93","author":"Queiroz","year":"2018","journal-title":"An. Bras. Dermatol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"309","DOI":"10.26440\/IHRJ\/0212.03.521060","article-title":"Recurrent Aphthous Ulcers (RAS) and Its Prevalence among People of Punjab","volume":"2","author":"Sharma","year":"2019","journal-title":"Int. Health Res. J."},{"key":"ref_72","first-page":"259","article-title":"Haematinic deficiency in recurrent aphthous stomatitis: Its prevalence and response to treatment","volume":"1","author":"Healy","year":"2004","journal-title":"Oral Biosci. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/0030-4220(93)90011-R","article-title":"Audit of diagnosis and investigations in patients with recurrent aphthous stomatitis","volume":"76","author":"Porter","year":"1993","journal-title":"Oral Surg. Oral Med. Oral Path."},{"key":"ref_74","first-page":"381","article-title":"Hematologic status in patients with recurrent aphthous stomatitis in Jordan","volume":"27","author":"Burgan","year":"2006","journal-title":"Saudi Med. J."},{"key":"ref_75","first-page":"453","article-title":"Psychological stress associated with aphthous ulcers and temporomandibular disorders","volume":"67","author":"Aslam","year":"2017","journal-title":"Pak. Armed Forces Med. J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/S0377-1237(02)80083-1","article-title":"Serum zinc levels in cutaneous disorders","volume":"58","author":"Arora","year":"2002","journal-title":"Med. J. Armed Forces India"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1385\/BTER:95:2:97","article-title":"Serum levels of vitamins A, C, and E, \u03b2-carotene, selenium, and zinc in patients with Beh\u00e7et\u2019s disease","volume":"95","author":"Erel","year":"2003","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_78","first-page":"2","article-title":"Comparisson of Serum zing level in recurrent patients and normal individuals","volume":"2","author":"Khademi","year":"2008","journal-title":"Dent. Res. J."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.jtemb.2013.04.002","article-title":"Copper\/zinc and copper\/selenium ratios, and oxidative stress as biochemical markers in recurrent aphthous stomatitis","volume":"27","author":"Ozturk","year":"2013","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_80","first-page":"81","article-title":"Effect of zinc-deficient diet on oral tissues and periodontal indices in rats","volume":"3","author":"Seyedmajidi","year":"2014","journal-title":"Int. J. Mol. Cell. Med."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"\u015alebioda, Z., Krawiecka, E., Szponar, E., and Dorocka-Bobkowska, B. (2017). Evaluation of serum zinc levels in patients with recurrent aphthous stomatitis (RAS). BMC Oral Health, 17.","DOI":"10.1186\/s12903-017-0450-x"},{"key":"ref_82","first-page":"60","article-title":"Effect of bioactive B12 in adhering discs on aphthous ulcers","volume":"4","author":"Burgess","year":"2008","journal-title":"Inside Dent."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3122\/jabfm.2009.01.080113","article-title":"Effectiveness of vitamin B12 in treating recurrent aphthous stomatitis: A randomized, double-blind, placebo-controlled trial","volume":"22","author":"Volkov","year":"2009","journal-title":"J. Am. Board Fam. Med."},{"key":"ref_84","first-page":"e5560695","article-title":"The Impact of DNA Methylation on IL6 mRNA Levels in Hematinic Deficiency and Atopy-Associated Recurrent Aphthous Stomatitis Patients","volume":"2021","author":"Gurnida","year":"2021","journal-title":"Int. J. Dent."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1111\/jop.12241","article-title":"Significant association of deficiencies of hemoglobin, iron, vitamin B12, and folic acid and high homocysteine level with recurrent aphthous stomatitis","volume":"44","author":"Sun","year":"2015","journal-title":"J. Oral Path. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"86","DOI":"10.29252\/cjhr.3.3.86","article-title":"Association of lifestyle and aphthous stomatitis among dentistry students","volume":"3","author":"Basirat","year":"2018","journal-title":"Casp. J. Health Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e2907812","DOI":"10.1155\/2018\/2907812","article-title":"Analysis of dietary related factors of recurrent aphthous stomatitis among college students","volume":"2018","author":"Du","year":"2018","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1002\/cre2.181","article-title":"Elevated serum insulin-like growth factor 1 in recurrent aphthous stomatitis","volume":"5","author":"Baccaglini","year":"2019","journal-title":"Clin. Exp. Dent. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1007\/s00784-020-03611-y","article-title":"Lifetime prevalence of recurrent aphthous stomatitis and its related factors in Northern Iranian population: The PERSIAN Guilan Cohort Study","volume":"25","author":"Darjani","year":"2021","journal-title":"Clin. Oral Investig."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"300060520976833","DOI":"10.1177\/0300060520976833","article-title":"Relationships of interleukin-17 polymorphisms with recurrent aphthous ulcer risk in a Han Chinese population","volume":"48","author":"Xiang","year":"2020","journal-title":"J. Int. Med. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1016\/j.jfma.2018.10.023","article-title":"Recurrent aphthous stomatitis\u2013Etiology, serum autoantibodies, anemia, hematinic deficiencies, and management","volume":"118","author":"Chiang","year":"2019","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1111\/iji.12228","article-title":"Association study of interleukin-1 family and interleukin-6 gene single nucleotide polymorphisms in recurrent aphthous stomatitis","volume":"42","author":"Najafi","year":"2015","journal-title":"Int. J. Immunogenet."},{"key":"ref_93","first-page":"290","article-title":"Strong association of antiepithelial cell antibodies with HLA-DR3 or DR7 phenotype in patients with recurrent oral ulcers","volume":"99","author":"Sun","year":"2000","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S1095-6433(01)00308-7","article-title":"Surfactant-associated proteins: Functions and structural variation","volume":"129","author":"Haagsman","year":"2001","journal-title":"Comp. Biochem. Physiol. A Mol. Integr. Physiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.jaci.2008.10.014","article-title":"Protective role of the lung collectins surfactant protein A and surfactant protein D in airway inflammation","volume":"122","author":"Haczku","year":"2008","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1111\/j.1399-0039.2009.01232.x","article-title":"Association between single nucleotide polymorphisms of surfactant protein D and allergic rhinitis in Chinese patients","volume":"73","author":"Deng","year":"2009","journal-title":"Tissue Antigens"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/j.1365-3083.2008.02187.x","article-title":"The additive contribution from inflammatory genetic markers on the severity of cardiovascular disease","volume":"69","author":"Berg","year":"2009","journal-title":"Scand. J. Immunol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/ejhg.2011.183","article-title":"Involvement of surfactant protein D in emphysema revealed by genetic association study","volume":"20","author":"Ishii","year":"2012","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Pueyo, N., Ortega, F.J., Mercader, J.M., Moreno-Navarrete, J.M., Sabater, M., Bonas, S., Botas, P., Delgado, E., Ricart, W., and Martinez-Larrad, M.T. (2013). Common genetic variants of surfactant protein-D (SP-D) are associated with type 2 diabetes. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060468"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"409","DOI":"10.3109\/15412555.2012.676110","article-title":"Association between genetic variations in surfactant protein d and emphysema, interstitial pneumonia, and lung cancer in a Japanese population","volume":"9","author":"Ishii","year":"2012","journal-title":"J. Chronic Obstr. Pulm. Dis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1007\/s00296-013-2904-z","article-title":"Smoking and polymorphisms of genes encoding mannose-binding lectin and surfactant protein-D in patients with rheumatoid arthritis","volume":"34","author":"Kristiansen","year":"2014","journal-title":"Rheumatol. Int."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1086\/315866","article-title":"Surfactant protein genetic marker alleles identify a subgroup of tuberculosis in a Mexican population","volume":"182","author":"Floros","year":"2000","journal-title":"J. Infect. Dis."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3899\/jrheum.140394","article-title":"Etiopathogenic role of surfactant protein D in the clinical and immunological expression of primary Sj\u00f6gren syndrome","volume":"42","author":"Arias","year":"2015","journal-title":"J. Rheumatol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"R57","DOI":"10.1186\/cc10030","article-title":"Influence of genetic variability at the surfactant proteins A and D in community-acquired pneumonia: A prospective, observational, genetic study","volume":"15","author":"Castro","year":"2011","journal-title":"Crit. Care."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e815727","DOI":"10.3389\/fgene.2022.815727","article-title":"SNP\u2013SNP Interactions of Surfactant Protein Genes in Persistent Respiratory Morbidity Susceptibility in Previously Healthy Children","volume":"13","author":"Gandhi","year":"2022","journal-title":"Front. Genet."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1111\/j.1469-1809.2011.00662.x","article-title":"Genetic Variants and Monoallelic Expression of Surfactant Protein-D in Inflammatory Bowel Disease","volume":"75","author":"Lin","year":"2011","journal-title":"Ann. Hum. Genet."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1002\/ibd.20936","article-title":"Genetic Variants inSurfactant, Pulmonary-associated Protein D (SFTPD) and Japanese Susceptibility to Ulcerative Colitis","volume":"15","author":"Tanaka","year":"2009","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e855","DOI":"10.6061\/clinics\/2019\/e855","article-title":"Association of surfactant-associated protein D gene polymorphisms with the risk of COPD: A meta-analysis","volume":"74","author":"Liao","year":"2019","journal-title":"Clinics"},{"key":"ref_109","first-page":"1137","article-title":"SNP rs3088308 is a risk factor for poor lung function in healthy smokers","volume":"66","author":"Shakoori","year":"2016","journal-title":"J. Pak. Med. Assoc."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/5\/1119\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:39:40Z","timestamp":1760125180000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/5\/1119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,22]]},"references-count":109,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["genes14051119"],"URL":"https:\/\/doi.org\/10.3390\/genes14051119","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,22]]}}}