Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Short Communication
  • Published:

Functional variations in MBL2 gene are associated with cutaneous leishmaniasis in the Amazonas state of Brazil

Genes & Immunity volume 16, pages 284–288 (2015)Cite this article

Subjects

Abstract

Functional variations in the mannose-binding lectin (MBL2) gene causing low levels of serum MBL are associated with susceptibility to numerous infectious diseases. We investigated whether there is genetic association of MBL2 variant alleles with cutaneous leishmaniasis (CL) caused by Leishmania guyanensis. We used PCR-restriction fragment length polymorphism to genotype six MBL2 variants, three in the promoter region and three in the exon 1. An association was noted between the single nucleotide polymorphism −221X/Y of the MBL2 gene and CL (P=2.9 × 10−6; odds ratio (OR)=1.9 (1.4–2.5) consistent with the hypothesis that the −221X allele confers high risk to development of CL among L. guyanensis-infected individuals. Furthermore, L. guyanensis-infected individuals bearing the codon 57 allele C had a higher risk of developing CL (P=5 × 10−5; OR=1.9 (1.4–2.6)). The low MBL expressor haplotype LXPB was also associated to CL (P=6 × 10−4). This study raises the possibility that functional polymorphisms in MBL2 gene play a role in clinical outcome of Leishmania infection.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Alvar J, Vélez ID, Bern C, Herrero M, Desjeux P, Cano J et al. Leishmaniasis worldwide and global estimates of its incidence. PLoS One 2012; 7: e35671.

    Article  CAS  Google Scholar 

  2. Hotez PJ, Remme JH, Buss P, Alleyne G, Morel C, Breman JG . Combating tropical infectious diseases: report of the Disease Control Priorities in Developing Countries Project. Clin Infect Dis 2004; 38: 871–878.

    Article  Google Scholar 

  3. Handman E, Elso C, Foote S . Genes and susceptibility to leishmaniasis. Adv Parasitol 2005; 59: 1–75.

    Article  Google Scholar 

  4. Grimaldi Jr G, Tesh RB . Leishmaniases of the New World: current concepts and implications for future research. Clin Microbiol Rev 1993; 6: 230–250.

    Article  Google Scholar 

  5. Marsden PD . Mucosal leishmaniasis (‘espundia’ Escomel, 1911). Trans R Soc Trop Med Hyg 1986; 80: 859–876.

    Article  CAS  Google Scholar 

  6. Castellucci L, Cheng LH, Araújo C, Guimarães LH, Lessa H, Machado P et al. Familial aggregation of mucosal leishmaniasis in northeast Brazil. Am J Trop Med Hyg 2005; 73: 69–73.

    Article  Google Scholar 

  7. Alcaïs A, Abel L, David C, Torrez ME, Flandre P, Dedet JP . Evidence for a major gene controlling susceptibility to tegumentary leishmaniasis in a recently exposed Bolivian population. Am J Hum Genet 1997; 61: 968–979.

    Article  Google Scholar 

  8. Castellucci LC, Almeida LF, Jamieson SE, Fakiola M, Carvalho EM, Blackwell JM . Host genetic factors in American cutaneous leishmaniasis: a critical appraisal of studies conducted in an endemic area of Brazil. Mem Inst Oswaldo Cruz 2014; 109: 279–288.

    Article  Google Scholar 

  9. Eisen DP, Minchinton RM . Impact of mannose-binding lectin on susceptibility to infectious diseases. Clin Infect Dis 2003; 37: 1496–1505.

    Article  CAS  Google Scholar 

  10. Ambrosio AR, De Messias-Reason IJ . Leishmania (Viannia) braziliensis: interaction of mannose-binding lectin with surface glycoconjugates and complement activation. An antibody-independent defence mechanism. Parasite Immunol 2005; 27: 333–340.

    Article  CAS  Google Scholar 

  11. Santos IK, Costa CH, Krieger H, Feitosa MF, Zurakowski D, Fardin B et al. Mannan-binding lectin enhances susceptibility to visceral leishmaniasis. Infect Immun 2001; 69: 5212–5215.

    Article  CAS  Google Scholar 

  12. Alonso DP, Ferreira AF, Ribolla PE, de Miranda Santos IK, do Socorro Pires e Cruz M, Aécio de Carvalho F et al. Genotypes of the mannan-binding lectin gene and susceptibility to visceral leishmaniasis and clinical complications. J Infect Dis 2007; 195: 1212–1217.

    Article  CAS  Google Scholar 

  13. Garred P, Madsen HO, Hofmann B, Svejgaard A . Increased frequency of homozygosity of abnormal mannan-binding-protein alleles in patients with suspected immunodeficiency. Lancet 1995; 346: 941–943.

    Article  CAS  Google Scholar 

  14. Summerfield JA, Ryder S, Sumiya M, Thursz M, Gorchein A, Monteil MA et al. Mannose binding protein gene mutations associated with unusual and severe infections in adults. Lancet 1995; 345: 886–889.

    Article  CAS  Google Scholar 

  15. Bellamy R, Ruwende C, McAdam KP, Thursz M, Sumiya M, Summerfield J et al. Mannose binding protein deficiency is not associated with malaria, hepatitis B carriage or tuberculosis in Africans. QJM 1998; 91: 13–18.

    Article  CAS  Google Scholar 

  16. Garred P, Richter C, Andersen AB, Madsen HO, Mtoni I, Svejgaard A et al. Mannan-binding lectin in the sub- Saharan HIV and tuberculosis epidemics. Scand J Immunol 1997; 46: 204–208.

    Article  CAS  Google Scholar 

  17. Hoal-Van Helden EG, Epstein J, Victor TC, Hon D, Lewis LA, Beyers N et al. Mannose-binding protein B allele confers protection against tuberculous meningitis. Pediatr Res 1999; 45: 459–464.

    Article  CAS  Google Scholar 

  18. Lipscombe RJ, Sumiya M, Hill AV, Lau YL, Levinsky RJ, Summerfield JA et al. High frequencies in African and non-African populations of independent mutations in the mannose binding protein gene. Hum Mol Genet 1992; 1: 709–715.

    Article  CAS  Google Scholar 

  19. Takahashi K, Gordon J, Liu H, Sastry KN, Epstein JE, Motwani M et al. Lack of mannose-binding lectin-A enhances survival in a mouse model of acute septic peritonitis. Microbes Infect 2002; 4: 773–784.

    Article  CAS  Google Scholar 

  20. Hamdi S, Ejghal R, Idrissi M, Ezzikouri S, Hida M, Soong L et al. A variant in the promoter of MBL2 is associated with protection against visceral leishmaniasis in Morocco. Infect Genet Evol 2013; 13: 162–167.

    Article  CAS  Google Scholar 

  21. Badaró R, Jones TC, Lorenço R, Cerf BJ, Sampaio D, Carvalho EM et al. A prospective study of visceral leishmaniasis in an endemic area of Brazil. J Infect Dis 1986; 154: 639–649.

    Article  Google Scholar 

  22. Locksley RM . Flying doctors. Nat Immunol 2000; 1: 457–458.

    Article  CAS  Google Scholar 

  23. Kamhawi S, Belkaid Y, Modi G, Rowton E, Sacks D . Protection against cutaneous leishmaniasis resulting from bites of uninfected sand flies. Science 2000; 290: 1351–1354.

    Article  CAS  Google Scholar 

  24. Anstead GM, Chandrasekar B, Zhao W, Yang J, Perez LE, Melby PC . Malnutrition alters the innate immune response and increases early visceralization following Leishmania donovani infection. Infect Immun 2001; 69: 4709–4718.

    Article  CAS  Google Scholar 

  25. Garcia L, Kindt A, Bermudez H, Llanos-Cuentas A, De Doncker S, Arevalo J et al. Culture-independent species typing of neotropical Leishmania for clinical validation of a PCR-based assay targeting heat shock protein 70 genes. J Clin Microbiol 2004; 42: 2294–2297.

    Article  CAS  Google Scholar 

  26. Marfurt J, Nasereddin A, Niederwieser I, Jaffe CL, Beck HP, Felger I . Identification and differentiation of Leishmania species in clinical samples by PCR amplification of the miniexon sequence and subsequent restriction fragment length polymorphism analysis. J Clin Microbiol 2003; 41: 3147–3153.

    Article  CAS  Google Scholar 

  27. Madsen HO, Garred P, Kurtzhals JA, Lamm LU, Ryder LP, Thiel S et al. A new frequent allele is the missing link in the structural polymorphism of the human mannan-binding protein. Immunogenetics 1994; 40: 37–44.

    Article  CAS  Google Scholar 

  28. Lipscombe RJ, Sumiya M, Summerfield JA, Turner MW . Distinct physicochemical characteristics of human mannose binding protein expressed by individuals of differing genotype. Immunology 1995; 85: 660–667.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Madsen HO, Garred P, Thiel S, Kurtzhals JA, Lamm LU, Ryder LP et al. Interplay between promoter and structural gene variants control basal serum level of mannan-binding protein. J Immunol 1995; 155: 3013–3020.

    CAS  PubMed  Google Scholar 

  30. Madsen HO, Satz ML, Hogh B, Svejgaard A, Garred P . Different molecular events result in low protein levels of mannan-binding lectin in populations from southeast Africa and South America. J Immunol 1998; 161: 3169–3175.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was funded by the Brazilian Council for Scientific and technological Development (CNPq) to RR (grant number: Processo 404181/2012-0).

Author information

Authors and Affiliations

  1. Faculdade de Medicina, Universidade Nilton Lins, Av. Prof Nilton Lins, Manaus, Brazil

    F J de Araujo, L D O da Silva, S A de Almeida, W de S Vital, S Talhari & R Ramasawmy

  2. Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil

    T G Mesquita, A Chrusciak-Talhari, J A de O Guerra & R Ramasawmy

Authors
  1. F J de Araujo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T G Mesquita
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L D O da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S A de Almeida
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. W de S Vital
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A Chrusciak-Talhari
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J A de O Guerra
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S Talhari
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. R Ramasawmy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R Ramasawmy.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on Genes and Immunity website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

de Araujo, F., Mesquita, T., da Silva, L. et al. Functional variations in MBL2 gene are associated with cutaneous leishmaniasis in the Amazonas state of Brazil. Genes Immun 16, 284–288 (2015). https://doi.org/10.1038/gene.2015.6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/gene.2015.6

Search

Advanced search

Quick links