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IL18 Gene Variants Influence the Susceptibility to Chagas Disease.

Leon Rodriguez DA, Carmona FD, Echeverría LE, González CI, Martin J - PLoS Negl Trop Dis (2016)

Bottom Line: This variant is located within the promoter region of the IL18 gene, and it has been described that it creates a binding site for the transcription factor OCT-1 affecting IL-18 expression levels.In addition, no evidence of association was observed between any of the analyzed IL18 gene polymorphisms and the development of CCC.In summary, our data suggest that genetic variation within the promoter region of IL18 is directly involved in the susceptibility to infection by T. cruzi, which provides novel insight into disease pathophysiology and adds new perspectives to achieve a more effective disease control.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, P.T.S., Granada, Spain.

ABSTRACT
Chagas disease is a parasitic disorder caused by the infection with the flagellated protozoan Trypanosoma cruzi. According to the World Health Organization, more than six million people are currently infected in endemic regions. Genetic factors have been proposed to influence predisposition to infection and development of severe clinical phenotypes like chronic Chagas cardiomyopathy (CCC). Interleukin 18 (IL18) encodes a proinflammatory cytokine that has been proposed to be involved in controlling T. cruzi infection. In this study, we analyzed the possible role of six IL18 gene variants (rs5744258, rs360722, rs2043055, rs187238, rs1946518 and rs360719), which cover most of the variation within the locus, in the susceptibility to infection by T. cruzi and/or CCC. In total, 1,171 individuals from a Colombian region endemic for Chagas disease, classified as seronegative (n = 595), seropositive asymptomatic (n = 175) and CCC (n = 401), were genotyped using TaqMan probes. Significant associations with T. cruzi infection were observed when comparing seronegative and seropositive individuals for rs187238 (P = 2.18E-03, OR = 0.77), rs360719 (P = 1.49E-03, OR = 0.76), rs2043055 (P = 2.52E-03, OR = 1.29), and rs1946518 (P = 0.0162, OR = 1.22). However, dependence analyses suggested that the association was mainly driven by the polymorphism rs360719. This variant is located within the promoter region of the IL18 gene, and it has been described that it creates a binding site for the transcription factor OCT-1 affecting IL-18 expression levels. In addition, no evidence of association was observed between any of the analyzed IL18 gene polymorphisms and the development of CCC. In summary, our data suggest that genetic variation within the promoter region of IL18 is directly involved in the susceptibility to infection by T. cruzi, which provides novel insight into disease pathophysiology and adds new perspectives to achieve a more effective disease control.

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Linkage disequilibrium D’ (A) and R-Squared (B) plots estimated by using expectation-maximization algorithm in Haploview V4.2.The analysis revealed that IL18 genetic variants were in strong LD.
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pntd.0004583.g001: Linkage disequilibrium D’ (A) and R-Squared (B) plots estimated by using expectation-maximization algorithm in Haploview V4.2.The analysis revealed that IL18 genetic variants were in strong LD.

Mentions: The six IL18 SNPs were in Hardy-Weinberg equilibrium in all the analyzed subgroups (P>0.01), suggesting that a possible inbreed in Guanentina and Comunera provinces is not likely. The genotyping success rate was over 95% and the allele frequencies in all cases were similar to those described for the Colombian population (CLM) of the 1000 genomes phase III project (http://www.1000genomes.org) [30]. A relatively high LD was observed throughout the gene in the analyzed population (Fig 1). Particularly, rs187238 and rs360719 showed an r2 value = 0.98, indicating that these two variants are almost completely linked and, consequently, they may be considered as the same marker for this study.


IL18 Gene Variants Influence the Susceptibility to Chagas Disease.

Leon Rodriguez DA, Carmona FD, Echeverría LE, González CI, Martin J - PLoS Negl Trop Dis (2016)

Linkage disequilibrium D’ (A) and R-Squared (B) plots estimated by using expectation-maximization algorithm in Haploview V4.2.The analysis revealed that IL18 genetic variants were in strong LD.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4814063&req=5

pntd.0004583.g001: Linkage disequilibrium D’ (A) and R-Squared (B) plots estimated by using expectation-maximization algorithm in Haploview V4.2.The analysis revealed that IL18 genetic variants were in strong LD.
Mentions: The six IL18 SNPs were in Hardy-Weinberg equilibrium in all the analyzed subgroups (P>0.01), suggesting that a possible inbreed in Guanentina and Comunera provinces is not likely. The genotyping success rate was over 95% and the allele frequencies in all cases were similar to those described for the Colombian population (CLM) of the 1000 genomes phase III project (http://www.1000genomes.org) [30]. A relatively high LD was observed throughout the gene in the analyzed population (Fig 1). Particularly, rs187238 and rs360719 showed an r2 value = 0.98, indicating that these two variants are almost completely linked and, consequently, they may be considered as the same marker for this study.

Bottom Line: This variant is located within the promoter region of the IL18 gene, and it has been described that it creates a binding site for the transcription factor OCT-1 affecting IL-18 expression levels.In addition, no evidence of association was observed between any of the analyzed IL18 gene polymorphisms and the development of CCC.In summary, our data suggest that genetic variation within the promoter region of IL18 is directly involved in the susceptibility to infection by T. cruzi, which provides novel insight into disease pathophysiology and adds new perspectives to achieve a more effective disease control.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, P.T.S., Granada, Spain.

ABSTRACT
Chagas disease is a parasitic disorder caused by the infection with the flagellated protozoan Trypanosoma cruzi. According to the World Health Organization, more than six million people are currently infected in endemic regions. Genetic factors have been proposed to influence predisposition to infection and development of severe clinical phenotypes like chronic Chagas cardiomyopathy (CCC). Interleukin 18 (IL18) encodes a proinflammatory cytokine that has been proposed to be involved in controlling T. cruzi infection. In this study, we analyzed the possible role of six IL18 gene variants (rs5744258, rs360722, rs2043055, rs187238, rs1946518 and rs360719), which cover most of the variation within the locus, in the susceptibility to infection by T. cruzi and/or CCC. In total, 1,171 individuals from a Colombian region endemic for Chagas disease, classified as seronegative (n = 595), seropositive asymptomatic (n = 175) and CCC (n = 401), were genotyped using TaqMan probes. Significant associations with T. cruzi infection were observed when comparing seronegative and seropositive individuals for rs187238 (P = 2.18E-03, OR = 0.77), rs360719 (P = 1.49E-03, OR = 0.76), rs2043055 (P = 2.52E-03, OR = 1.29), and rs1946518 (P = 0.0162, OR = 1.22). However, dependence analyses suggested that the association was mainly driven by the polymorphism rs360719. This variant is located within the promoter region of the IL18 gene, and it has been described that it creates a binding site for the transcription factor OCT-1 affecting IL-18 expression levels. In addition, no evidence of association was observed between any of the analyzed IL18 gene polymorphisms and the development of CCC. In summary, our data suggest that genetic variation within the promoter region of IL18 is directly involved in the susceptibility to infection by T. cruzi, which provides novel insight into disease pathophysiology and adds new perspectives to achieve a more effective disease control.

Show MeSH
Related in: MedlinePlus