Mannose-Binding Lectin Gene Polymorphism versus Microbial Virulence in the Pathogenesis of Vulvovaginal Candidiasis and Recurrent Vulvovaginal Candidiasis

Iman Wali; Eman M. Haggag; Alaa R. Awad; Mohammad A. El-Sharkawy; Marwa K. Sallam

doi:10.3889/oamjms.2023.8261

Authors

Iman Wali Department of Medical Microbiology and Immunology https://orcid.org/0000-0002-0913-7172
Eman M. Haggag Department of Medical Microbiology and Immunology, Faculty of Medicine, Cairo University, Kasr Al Ainy Hospitals, Cairo, Egypt
Alaa R. Awad Department of Medical Microbiology and Immunology, Faculty of Medicine, Cairo University, Kasr Al Ainy Hospitals, Cairo, Egypt
Mohammad A. El-Sharkawy Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, Kasr Al Ainy Hospitals, Cairo, Egypt
Marwa K. Sallam Department of Medical Microbiology and Immunology, Faculty of Medicine, Cairo University, Kasr Al Ainy Hospitals, Cairo, Egypt; Department of Basic Medical Sciences, Faculty of Medicine, King Salman International University (KSIU), El-Tor, Egypt https://orcid.org/0000-0001-5281-1727

DOI:

https://doi.org/10.3889/oamjms.2023.8261

Keywords:

Candida, virulence, Mannose Binding Lectin, Gene polymorphism, Vulvovaginal candidiasis, recurrent, D-ARMs, esterase, phospholipase, Biofilm

Abstract

BACKGROUND: Vulvovaginal candidiasis (VVC) is one of the most common infections affecting women.

AIM: This study aimed to determine MBL2 polymorphism frequency among females with VVC together with assessment of Candida virulence attributes in the pathogenesis of it.

METHODS: Fifty Egyptian patients and 50 controls were included in the study. Vaginal swabs were cultured to identify Candida spp. D-ARMs were used to determine MBL2 polymorphism.

RESULTS: Cases with VVC revealed Candida albicans 37(74%) and non-Albicans Candida (NAC) 13 (26%) with a significant difference between C. albicans and NAC esterase and phospholipase. Thirty C. albicans isolates (81.1%) possessed three or more virulence factors, compared to only four NAC (30.8%) (p = 0.002). As regards MBL2 polymorphism, the X allele was found to be significantly high in cases than in controls (p ≤ 0.001). B allele on codon 54 and L allele on promoter region was more in cases. Other haplotypes were more in cases than controls with a significant difference for LXQB and HXQB. HXPB and LXQB were detected among recurrent VVC (RVVC) cases more than VVC cases.

CONCLUSION: RVVC appears to be a multi-factorial disorder; hence, treatment should be individualized. Recombinant MBL may be considered in the future treatment of RVVC in the case of associated genetic MBL2 polymorphism.

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References

Forsum U, Holst E, Larsson PG, Vasquez A, Jakobsson T, Mattsby-Baltzer I. Bacterial vaginosis-a microbiological and immunological enigma. APMIS. 2005;113(2):81-90. https://doi.org/10.1111/j.1600-0463.2005.apm1130201.x DOI: https://doi.org/10.1111/j.1600-0463.2005.apm1130201.x

Wojitani MD, de Aguiar LM, Baracat EC, Linhares IM. Association between mannose-binding lectin and interleukin-1 receptor antagonist gene polymorphisms and recurrent vulvovaginal candidiasis. Arch Gynecol Obstet. 2012;285(1):149-53. https://doi.org/10.1007/s00404-011-1920-z PMid: 21655939 DOI: https://doi.org/10.1007/s00404-011-1920-z

Bleicher J, Stockdale CK. Association between recurrent bacterial vaginosis and Helicobacter pylori infection: A case report. Proc Obstet Gynecol. 2015;5(2):1-6. https://doi.org/10.17077/2154-4751.1289 DOI: https://doi.org/10.17077/2154-4751.1289

Sobel JD. Recurrent vulvovaginal candidiasis. Am J Obstet Gynecol. 2016;214(1):15-21. https://doi.org/10.1016/j.ajog.2015.06.067 PMid:26164695 DOI: https://doi.org/10.1016/j.ajog.2015.06.067

Puel A, Cypowyj S, Marodi L, Abel L, Picard C, Casanova JL. Inborn errors of human IL-17 immunity underlie chronic mucocutaneous candidiasis. Curr Opin Allergy Clin Immunol. 2012;12(6):616-22. https://doi.org/10.1097/ACI.0b013e328358cc0b PMid:23026768 DOI: https://doi.org/10.1097/ACI.0b013e328358cc0b

ElFeky DS, Gohar NM. Evaluation of virulence factors of Candida species isolated from superficial versus systematic Candidiasis. Egypt J Med Microbiol. 2016;25(1):27-36. https://doi.org/10.12816/0037089 7. Kasperkiewicz K, Swierzko AS, Bartlomiejczyk MA, Cedzynski M, Noszczynska M, Duda KA, et al. Interaction of human mannose-binding lectin (MBL) with Yersinia enterocolitica lipopolysaccharide. Int J Med Microbiol. 2015;305(6):544-52. https://doi.org/10.1016/j.ijmm.2015.07.001 PMid:26188838 DOI: https://doi.org/10.1016/j.ijmm.2015.07.001

Mashaly GE, El-Sabbagh AM, El-Kazzaz SS, Nour I. MBL2 gene polymorphism and the association with neonatal sepsis in Egyptian neonates, a case control study. Open J Immunol. 2016;6(3):111-9. https://doi.org/10.4236/oji.2016.63012 DOI: https://doi.org/10.4236/oji.2016.63012

Larsen F, Madsen HO, Sim RB, Koch C, Garred P. Disease-associated mutations in human mannose-binding lectin compromise oligomerization and activity of the final protein. J Biol Chem. 2004;279(20):21302-11. https://doi.org/10.1074/jbc.M400520200 PMid:14764589 DOI: https://doi.org/10.1074/jbc.M400520200

Kalia N, Singh J, Sharma S, Arora H, Kaur M. Genetic and phenotypic screening of mannose-binding lectin in relation to risk of recurrent vulvovaginal infections in women of North India: A prospective cohort study. Front Microbiol. 2017;8:75. https://doi.org/10.3389/fmicb.2017.00075 PMid:28197138 DOI: https://doi.org/10.3389/fmicb.2017.00075

Garred P, Larsen F, Seyfarth J, Fujita R, Madsen HO. Mannose-binding lectin and its genetic variants. Genes Immun. 2006;7(2):85-94. https://doi.org/10.1038/sj.gene.6364283 PMid:16395391 DOI: https://doi.org/10.1038/sj.gene.6364283

Pradhan V, Surve P, Rajadhyaksha A, et al. Mannose binding lectin (MBL) 2 gene polymorphism and its association with clinical manifestations in systemic lupus erythematosus (SLE) patients from western India. Indian J Med Res. 2015;141(2):199-204. https://doi.org/10.4103/0971-5916.155558 PMid:25900955 DOI: https://doi.org/10.4103/0971-5916.155558

Moghadam SA, Bazi A, Miri-Moghaddam M, Miri-Moghaddam E. Mannose binding lectin-2 gene functional polymorphisms in chronic periodontitis patients; a report from Iran. Meta Gene. 2018;17:128-31. https://doi.org/10.1016/j.mgene.2018.05.080 DOI: https://doi.org/10.1016/j.mgene.2018.05.080

Centers for Disease Control and Prevention (CDC). 2015 Diseases Characterized by Vaginal Discharge: VVC. Sexually Transmitted Diseases Treatment. Guidelines; 2015. Available from: https://www.cdc.gov/std/tg2015/candidiasis.htm [Last accessed on 2017 Aug].

Cauchie M, Desmet S, Lagrou K. Candida and its dual lifestyle as a commensal and a pathogen. Res Microbiol. 2017;168(9- 10):802-10. https://doi.org/10.1016/j.resmic.2017.02.005 PMid:28263903 DOI: https://doi.org/10.1016/j.resmic.2017.02.005

Aniebue U, Nwankwo TO, Nwafor MI. Vulvovaginal candidiasis in reproductive age women in Enugu Nigeria, clinical versus laboratory-assisted diagnosis. Niger J Clin Pract. 2018;21(8):1017-22. https://doi.org/10.4103/njcp.njcp_25_16 PMid:30074004 DOI: https://doi.org/10.4103/njcp.njcp_25_16

Deorukhkar SC, Roushani S. Identification of Candida species: Conventional methods in the era of molecular diagnosis. Ann Microbiol Immunol. 2018;1(1):1002.

Deepa K, Jeevitha T, Michael A. In vitro evaluation of virulence factors of Candida species isolated from oral cavity. J Microbiol Antimicrob. 2015;7(3):28-32. https://doi.org/10.5897/JMA2015.0337 DOI: https://doi.org/10.5897/JMA2015.0337

Inci M, Atalay M, Koç A, Yula E, Evirgen O, Durma S, et al. Investigating virulence factors of clinical Candida isolates in relation to atmospheric conditions and genotype. Turk J Med Sci. 2012;42(2):1476-83. https://doi.org/10.3906/sag-1204-119 DOI: https://doi.org/10.3906/sag-1204-119

Fatahinia M, Halvaeezadeh M, Rezaei-Matehkolaei A. Comparison of enzymatic activities in different Candida species isolated from women with vulvovaginitis. J Mycol Méd. 2017;27(2):188-94. https://doi.org/10.1016/j.mycmed.2017.01.009 PMid:28236530 DOI: https://doi.org/10.1016/j.mycmed.2017.01.009

Vidotto V, Ponton J, Aoki S, Quindós G, Mantoanm B, Pugliese A, et al. Differences in extracellular enzymatic activity between Candida dubliniensis and Candida albicans isolates. Rev Iberoam Micol. 2004;21(2):70-4. PMid:15538830

Chan Y. Biostatistics 103: Qualitative data-tests of independence. Singapore Med J. 2003;44(10):498-503.

ElFeky DS, Gohar NM, El-Seidi EA, Ezzat MM, AboElew SH. Species identification and antifungal susceptibility pattern of Candida isolates in cases of vulvovaginal candidiasis. Alex J Med. 2016;52(3):269-77. https://doi.org/10.1016/j.ajme.2015.10.001 DOI: https://doi.org/10.1016/j.ajme.2015.10.001

Mtibaa L, Fakhfakh N, Kallel A, Belhadj S, Salah NB, Bada N, et al. Vulvovaginal candidiasis: Etiology, symptomatology and risk factors. J Mycol Méd. 2017;27(2):153-8. https://doi.org/10.1016/j.mycmed.2017.01.003 PMid:28314677 DOI: https://doi.org/10.1016/j.mycmed.2017.01.003

Sangaré I, Sirima C, Bamba S, Zida A, Cissé M, Bazié WW, et al. Prevalence of vulvovaginal candidiasis in pregnancy at three health centers in Burkina Faso. J Mycol Méd. 2018;28(1):186- 92. https://doi.org/10.1016/j.mycmed.2017.08.006 PMid:28939305 DOI: https://doi.org/10.1016/j.mycmed.2017.08.006

Ghaddar N, El Roz A, Ghssein G, Ibrahim JN. Emergence of vulvovaginal candidiasis among Lebanese pregnant women: Prevalence, risk factors, and species distribution. Infect Dis Obstet Gynecol. 2019;2019:5016810. https://doi.org/10.1155/2019/5016810 PMid:31467477 DOI: https://doi.org/10.1155/2019/5016810

Babic M, Hukic M. Candida albicans and non-albicans species as etiological agent of vaginitis in pregnant and non-pregnant women. Bosn J Basic Med Sci. 2010;10(1):89-97. https://doi.org/10.17305/bjbms.2010.2744 PMid:20192939 DOI: https://doi.org/10.17305/bjbms.2010.2744

Babin D, Kotigadde S, Rao P, Rao TV. Clinico-mycological profile of vaginal candidiasis in a tertiary care hospital in Kerala. Int J Res Biol Sci. 2013;3(1):55-9.

Ismail DK, Haleim MM, El-Feky EA, Sayed A, Sayed AM, et al. Prevalence of non albicans species associated with vulvovaginal candidiasis in Egyptian women. Int J Adv Int Health Sci. 2015;l2(3):304-13.

Gonçalves B, Ferreira C, Alves CT, Henriques M, Azeredo J, Silva S. Vulvovaginal candidiasis: Epidemiology, microbiology and risk factors. Crit Rev Microbiol. 2016;42(6):905-27. https://doi.org/10.3109/1040841X.2015.1091805 PMid:26690853 DOI: https://doi.org/10.3109/1040841X.2015.1091805

Brandolt T, Klafke GB, Gonçalves CV, Bitencourt LR, de Martinez AM, Mendes JF, et al. Prevalence of Candida spp. in cervical-vaginal samples and the in vitro susceptibility of isolates. Braz J Microbiol. 2017;48(1):145-50. https://doi.org/10.1016/j.bjm.2016.09.006 PMid:27756539 DOI: https://doi.org/10.1016/j.bjm.2016.09.006

Seifi Z, Mahmoudabadi AZ, Zarrin M. Extracellular enzymes and susceptibility to fluconazole in Candida strains isolated from patients with vaginitis and healthy individuals. Jundishapur J Microbiol. 2015;8(3):e20162. https://doi.org/10.5812/jjm.20162 PMid:25861438 DOI: https://doi.org/10.5812/jjm.20162

Fornari G, Vicente V, Gomes RR, Muro MD, Pinheiro RL, Ferrari C, et al. Susceptibility and molecular characterization of Candida species from patients with vulvovaginitis. Braz J Microbiol. 2016;47(2):373-80. https://doi.org/10.1016/j.bjm.2016.01.005 PMid:26991298 DOI: https://doi.org/10.1016/j.bjm.2016.01.005

Yassin M, Mostafa A, Al-Askar A, Bdeer R. In vitro antifungal resistance profile of Candida strains isolated from Saudi women suffering from vulvovaginitis. Eur J Med Res. 2020;25(1):1. https://doi.org/10.1186/s40001-019-0399-0 PMid:31901238 DOI: https://doi.org/10.1186/s40001-019-0399-0

Makanjuola O, Bongomin F, Fayemiwo SA. An update on the roles of non-albicans Candida species in vulvovaginitis. J Fungi (Basel). 2018;4(4):121. https://doi.org/10.3390/jof4040121 PMid:30384449 DOI: https://doi.org/10.3390/jof4040121

Ghaddar N, Anastasiadis E, Halimeh R, Ghaddar A, Dhar R, AlFouzan W, et al. Prevalence and antifungal susceptibility of Candida albicans causing vaginal discharge among pregnant women in Lebanon. BMC Infect Dis. 2020;20(1):32. https://doi.org/10.1186/s12879-019-4736-2 PMid:31931738 DOI: https://doi.org/10.1186/s12879-019-4736-2

Konate A, Yavo W, Kassi FK, Djohan V, Angora EK, Barro- Kiki PC, et al. Aetiologies and contributing factors of vulvovaginal candidiasis in Abidjan (Côte d’Ivoire). J Mycol Med. 2014;24:93- 9. https://doi.org/10.1016/j.mycmed.2013.11.006 PMid:24387809 DOI: https://doi.org/10.1016/j.mycmed.2013.11.006

Ameen F, Moslem M, Al Tami M, Al-Ajlan H, Al-Qahtani N. Identification of Candida species in vaginal flora using conventional and molecular methods. J Mycol Med. 2017;27(3):364-8. https://doi.org/10.1016/j.mycmed.2017.04.105 PMid:28578925 DOI: https://doi.org/10.1016/j.mycmed.2017.04.105

Noori M, Dakhili M, Sepahvand A, Davari N. Evaluation of esterase and hemolysin activities of different Candida species isolated from vulvovaginitis cases in Lorestan Province, Iran. Curr Med Mycol. 2017;3(4):1-5. https://doi.org/10.29252/ cmm.3.4.1 PMid:29707672 DOI: https://doi.org/10.29252/cmm.3.4.1

Kumar H, Kawai T, Akira S. Pathogen recognition by the innate immune system. Int Rev Immunol. 2011;30(1):16-34. https://doi.org/10.3109/08830185.2010.529976 PMid:21235323 DOI: https://doi.org/10.3109/08830185.2010.529976

Pakshir K, Zomorodian K, Karamitalab M, Jafari M, Taraz H, Ebrahimi H. Phospholipase, esterase and hemolytic activities of Candida spp. isolated from onychomycosis and oral lichen planus lesions. J Mycol Med. 2013;23(2):113-8. https://doi.org/10.1016/j.mycmed.2013.04.007 PMid:23706304 DOI: https://doi.org/10.1016/j.mycmed.2013.04.007

Malcok H, Aktas E, Ayyildiz A, Yigit N, Yazgi H. Hemolytic activities of the Candida species in liquid medium. Eurasian J Med. 2009;41(2):95-8. PMid:25610076

Rossoni RD, Barbosa JO, Vilela SF, Jorge AO, Junqueira JC. Comparison of the hemolytic activity between C. albicans and non-albicans Candida species. Braz Oral Res. 2013;27(6):484- 9. https://doi.org/10.1590/S1806-83242013000600007 PMid:24346046 DOI: https://doi.org/10.1590/S1806-83242013000600007

Pereira CA, Domingues N, Araújo MI, Junqueira JC, Back- Brito GN, Jorge AO. Production of virulence factors in Candida strains isolated from patients with denture stomatitis and control individuals. Diagn Microbiol Infect Dis. 2016;85(1):66-72. https://doi.org/10.1016/j.diagmicrobio.2016.01.014 PMid:26971635 DOI: https://doi.org/10.1016/j.diagmicrobio.2016.01.014

De Melo Riceto ÉB, de Paula Menezes R, Penatti MP, Pedroso RD. Enzymatic and hemolytic activity in different Candida species. Rev Iberoam Micol. 2015;32(2):79-82. https://doi.org/10.1016/j.riam.2013.11.003 PMid:24704439 DOI: https://doi.org/10.1016/j.riam.2013.11.003

Moharram A, Abdel-Ati M, Othman EM. Vaginal yeast infection in patients admitted to Al-Azhar university hospital, Assiut, Egypt. J Basic Appl Mycol. 2013;4:21-32.

Oksuz S, Sahin I, Yildirim M, Gulcan A, Yavuz T, Kaya D, et al. Phospholipase and proteinase activities in different Candida species isolated from anatomically distinct sites of healthy adults. Jpn J Infect Dis. 2007;60(5):280-3. PMid:17881867

Mohan das V, Ballal M. Proteinase and phospholipase activity as virulence factors in Candida species isolated from blood. Rev Iberoam Micol. 2008;25(4):208-10. https://doi.org/10.1016/s1130-1406(08)70050-0 PMid:19071887 DOI: https://doi.org/10.1016/S1130-1406(08)70050-0

Pinto E, Ribeiro IC, Ferreira NJ, Fortes CE, Fonseca PA, Figueiral MH. Correlation between enzyme production, germ tube formation and susceptibility to fluconazole in Candida species isolated from patients with denture-related stomatitis and control individuals. J Oral Pathol Med. 2008;37(10):587-92. https://doi.org/10.1111/j.1600-0714.2008.00687.x PMid:18764856 DOI: https://doi.org/10.1111/j.1600-0714.2008.00687.x

Demirbilek M, Timurkaynak F, Can F, Azap O, Arslan H. Biofilm production and antifungal susceptibility patterns of Candida species isolated from hospitalized patients. Mikrobiyol Bul. 2007;41(2):261-9. PMid:17682713

Dabiri S, Shams-Ghahfarokhi M, Razzaghi-Abyaneh M. Comparative analysis of proteinase, phospholipase, hydrophobicity and biofilm forming ability in Candida species isolated from clinical specimens. J Mycol Med. 2018;28(3):437- 42. https://doi.org/10.1016/j.mycmed.2018.04.009 PMid:29778633 DOI: https://doi.org/10.1016/j.mycmed.2018.04.009

Rosati D, Bruno M, Jaeger M, Oever TJ, Netea MG. Recurrent vulvovaginal candidiasis: An immunological perspective. Microorganisms. 2020;8(2):144. https://doi.org/10.3390/microorganisms8020144 PMid:31972980 DOI: https://doi.org/10.3390/microorganisms8020144

Jaeger M, Plantinga T, Joosten LA, Kullberg BJ, Netea MG. Genetic basis for recurrent vulvo-vaginal candidiasis. Curr Infect Dis Rep. 2013;15(2):136-42. https://doi.org/10.1007/s11908-013-0319-3 PMid:23354953 DOI: https://doi.org/10.1007/s11908-013-0319-3

Hammad NM, El Badawy NE, Nasr AM, Ghramh HA. Mannose-binding lectin gene polymorphism and its association with susceptibility to recurrent vulvovaginal candidiasis. Biomed Res Int. 2018;2018:7648152. https://doi.org/10.1155/2018/7648152 PMid:29850562 DOI: https://doi.org/10.1155/2018/7648152

Wächtler B, Citiulo F, Jablonowskietal N. Candida albicans-epithelial interactions: Dissecting the roles of active penetration, induced endocytosis and host factors on the infection process. PLoS One. 2012;7(5):e36952. https://doi.org/10.1371/journal.pone.0036952 PMid:22606314 DOI: https://doi.org/10.1371/journal.pone.0036952

Ip WK, Lau YL. Role of mannose-binding lectin in the innate defense against Candida albicans: Enhancement of complement activation, but lack of opsonic function, in phagocytosis by human dendritic cells. J Infect Dis. 2004;190(3):632-40. https://doi.org/10.1086/422397 PMid:15243942 DOI: https://doi.org/10.1086/422397

Shawky R, Abd El-Fattah S, Kamal TM, Esa MA, El Nady GH. Genotyping of mannose-binding lectin MBL2 codon 54 and promoter alleles in Egyptian infants with acute respiratory tract infections. Egypt J Med Hum Genet. 2014;15(1):31-8. https:// doi.org/10.1016/j.ejmhg.2013.10.002 DOI: https://doi.org/10.1016/j.ejmhg.2013.10.002

Ocejo-Vinyals JG, Lavin-Alconero L, Sanchez-Velasco P, Guerrero-Alonso MA, Ausín F, Fariñas MC, et al. Mannose-binding lectin promoter polymorphisms and gene variants in pulmonary tuberculosis patients from Cantabria (northern Spain). 2012;2012:469128. https://doi.org/10.1155/2012/469128 PMid:23304495 DOI: https://doi.org/10.1155/2012/469128

Babula O, Lazdane G, Kroica J, Ledger WJ, Witkin SS. Relation between recurrent vulvovaginal candidiasis, vaginal concentrations of mannose-binding lectin, and a mannose-binding lectin gene polymorphism in Latvian women. Clin Infect Dis. 2003;37(5):733-7. https://doi.org/10.1086/377234 PMid:12942410 DOI: https://doi.org/10.1086/377234

Liu F, Liao Q, Liu Z. Mannose-binding lectin and vulvovaginal candidiasis. Int J Gynecol Obstet. 2006;92(1):43-7. https://doi.org/10.1016/j.ijgo.2005.08.024 PMid:16256117 DOI: https://doi.org/10.1016/j.ijgo.2005.08.024

Giraldo PC, Babula O, Gonçalves AK, Linhares IM, Amaral RL, Ledger WJ, et al. Mannose-binding lectin gene polymorphism, vulvovaginal candidiasis, and bacterial vaginosis. Obstet Gynecol. 2007;109(5):1123-28. https://doi.org/10.1097/01.AOG.0000260386.17555.a5 PMid:17470593 DOI: https://doi.org/10.1097/01.AOG.0000260386.17555.a5

Esmat S, Omran D, Sleem GA, Rashed L. Serum mannan-binding lectin in Egyptian patients with chronic hepatitis C: Its relation to disease progression and response to treatment. Hepat Mon. 2012;12(4):259-64. https://doi.org/10.5812/hepatmon.704 PMid:22690233 DOI: https://doi.org/10.5812/hepatmon.704

Tao R, Hua CZ, Hu YZ, Shang SQ. Genetic polymorphisms and serum levels of mannose-binding lectin in Chinese pediatric patients with common infectious diseases. Int J Infect Dis. 2012;16(5):e403-7. https://doi.org/10.1016/j.ijid.2012.01.014 PMid:22444663 DOI: https://doi.org/10.1016/j.ijid.2012.01.014

Donders G, Slabbaert K, Vancalsteren K, Pelckmans S, Bellen G. Can vaginal pH be measured from the wet mount slide? Eur J Obstet Gynecol Reprod Biol. 2009;146(1):100-3. https://doi.org/10.1016/j.ejogrb.2009.06.002 PMid:19643525 DOI: https://doi.org/10.1016/j.ejogrb.2009.06.002

Nedović B, Posteraro B, Leoncini E, Ruggeri A, Amore R, Sanguinetti M, et al. Mannose-binding lectin codon 54 gene polymorphism and vulvovaginal candidiasis: A systematic review and meta-analysis. Biomed Res Int. 2014;2014:738298. https://doi.org/10.1155/2014/738298 PMid:25143944 DOI: https://doi.org/10.1155/2014/738298

Verdu P, Barreiro LB, Patin E, Gessain A, Cassar O, Kidd JR, et al. Evolutionary insights into the high worldwide prevalence of MBL2 deficiency alleles. Hum Mol Genet. 2006;15(17):2650-8. https://doi.org/10.1093/hmg/ddl193 PMid:16885193 DOI: https://doi.org/10.1093/hmg/ddl193

Oudshoorn AM, van den Dungen FM, Bach KP, Koomen I, Fetter WP, Catsburg A, et al. Mannose-binding lectin in term newborns and their mothers: Genotypic and phenotypic relationship. Hum Immunol. 2008;69(6):344-8. https://doi.org/10.1016/j.humimm.2008.04.010 PMid:18571005 DOI: https://doi.org/10.1016/j.humimm.2008.04.010

Jha A, Sundaravadivel P, Singh VK, Pati SS, Patra PK, Kremsner PG, et al. MBL2 variations and malaria susceptibility in Indian populations. Infect Immun. 2014;82(1):52-61. https://doi.org/10.1128/IAI.01041-13 PMid:24126531 DOI: https://doi.org/10.1128/IAI.01041-13