Genotyping of IL-10, TNFα and TLR4 gene polymorphisms in individuals with asymptomatic and chronic cutaneous leishmaniasis caused by Leishmania (Viannia)
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1
CIDEIM, Colombia
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2
Universidad ICESI, Facultad de Ciencias Naturales Departamento de Ciencias Biologicas, Colombia
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3
CIDEIM, Colombia
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4
CIDEIM, Colombia
The spectrum of clinical manifestations caused by Leishmania (Viannia) ranges from asymptomatic infection to self-limited cutaneous lesions that resolve without therapy, or chronic (non-healing) manifestations lasting several years and often not responsive to conventional chemotherapy. Given the critical role of the immune response in the outcome of the cutaneous leishmaniasis (CL) caused by L. (Viannia), it is plausible that functional polymorphisms in immune-related genes contribute in defining the outcome of human infection. A high frequency of single nucleotide polymorphisms (SNPs) TNFα, IL-10 and TLR4 genes has been found in patients with CL, suggesting a role in susceptibility and severity of the disease.
The aim of this study was to determine the frequency of SNPs in TNFα, IL-10 and TLR4 genes and to explore its relationship with the clinical outcome in individuals with asymptomatic infection and chronic CL (representing clinical resistance and susceptibility to infection, respectively). This study was approved and monitored by the institutional ethics committee. DNA samples were obtained from buccal swabs of adult Afro-American patients with chronic CL (n=38) and asymptomatic individuals (n=43). All study participants were residents of rural endemic areas of L. (V.) panamensis transmission in the Colombian South-Pacific. Genotyping of TNFα -308G/A (rs1800629), IL-10 -819C/T (rs1800871), and TLR4 SNPs, Asp299Gly (A/G) (rs4986790) and Thr399Ile (C/T) (rs4986791), was conducted by PCR-restriction fragment length polymorphisms. Chi-square or Fisher’s exact test was used to determine differences between allele and genotype frequencies.
The distribution of the genotypic variants for the evaluated SNPs met the Hardy-Weinberg equilibrium (p > 0.05). Distribution of the A allele in TNFα rs1800629 was found more frequently in individuals with asymptomatic infection (15% vs 7.5%), whereas the CC genotype in IL-10 rs1800871 was more frequent in patients with CCL (34%) compared to those with asymptomatic infection (25%). These differences were not statistically significant. No differences in TLR4 polymorphisms frequencies were found among groups for either rs4986790 or rs4986791 SNPs. Additional stratification by sex did not allow any relationship to be established.
In this study, genotyping of four independent gene variants was conducted in an attempt to overcome the limitations of single gene polymorphism studies previously reported for CL. However, no differences in SNP frequencies between groups were found. Strikingly, allele frequencies for TLR4 gene reported in this study were lower than the ones reported previously in other Colombian populations. This pilot study provides a reference base for the design of robust analyses of genetic polymorphisms in immune response genes in the South-Pacific Afro-descendent Colombian population.
Acknowledgements
We gratefully acknowledge the support of the CIDEIM BioBank personnel, especially Maryori Vidarte and Alejandra Arcos for provision of samples. Research reported in this study was supported by the Fogarty International Center of the National Institutes of Health under Award Number D43TW006589.
Keywords:
Leishmania,
snps,
TLR4,
TNFalpha,
IL-10,
Cytokines
Conference:
IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología, Medellin, Colombia, 13 Oct - 16 Oct, 2015.
Presentation Type:
Poster Presentation
Topic:
Infectious and parasitic diseases
Citation:
Mera Ramirez
A,
Castillo
A,
Orobio
Y,
Gomez
MA and
Gallego
C
(2015). Genotyping of IL-10, TNFα and TLR4 gene polymorphisms in individuals with asymptomatic and chronic cutaneous leishmaniasis caused by Leishmania (Viannia).
Front. Immunol.
Conference Abstract:
IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología.
doi: 10.3389/conf.fimmu.2015.05.00186
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Received:
29 May 2015;
Published Online:
14 Sep 2015.
*
Correspondence:
PhD. Carolina Gallego, CIDEIM, Cali, Valle, Colombia, cgallego@cideim.org.co