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The -2518bp promoter polymorphism at CCL2/MCP1 influences susceptibility to mucosal but not localized cutaneous leishmaniasis in Brazil
Journal article   Peer reviewed

The -2518bp promoter polymorphism at CCL2/MCP1 influences susceptibility to mucosal but not localized cutaneous leishmaniasis in Brazil

Rajendranath Ramasawmy, Eliane Menezes, Andrea Magalhães, Joyce Oliveira, Léa Castellucci, Roque Almeida, Maria Elisa A Rosa, Luiz Henrique Guimarães, Marcus Lessa, Elza Noronha, …
Infection, genetics and evolution, Vol.10(5), pp.607-613
07/2010
DOI: 10.1016/j.meegid.2010.04.006
PMCID: PMC2878927
PMID: 20430117
url
http://www.sciencedirect.com/science/article/pii/S1567134810001048View
Open Access

Abstract

Mucosal leishmaniasis (ML) follows localized cutaneous leishmaniasis (CL) caused by Leishmania braziliensis. Proinflammatory responses mediate CL self-healing but are exaggerated in ML. Proinflammatory monocyte chemoattractant protein 1 (MCP-1; encoded by CCL2) is associated with CL. We explore its role in CL/ML through analysis of the regulatory CCL2 -2518bp promoter polymorphism in CL/ML population samples and families from Brazil. Genotype frequencies were compared among ML/CL cases and control groups using logistic regression and the family-based association test (FBAT). MCP-1 was measured in plasma and macrophages. The GG recessive genotype at CCL2 -2518bp was more common in patients with ML (N=67) than in neighborhood control (NC; N=60) subjects (OR 1.78; 95% CI 1.01-3.14; P=0.045), than in NC combined with leishmanin skin-test positive (N=60) controls (OR 4.40; 95% CI 1.42-13.65; P=0.010), and than in controls combined with CL (N=60) patients (OR 2.78; 95% CI 1.13-6.85; P=0.045). No associations were observed for CL compared to any groups. FBAT (91 ML and 223 CL cases in families) confirmed recessive association of ML with allele G (Z=2.679; P=0.007). Higher levels of MCP-1 occurred in plasma (P=0.03) and macrophages (P<0.0001) from GG compared to AA individuals. These results suggest that high MCP-1 increases risk of ML.
Brazil Leishmania braziliensis Leishmaniasis, Mucocutaneous - immunology Genetic Predisposition to Disease Genetic Association Studies Gene Frequency Humans Middle Aged Chemokine CCL2 - genetics Genotype Leishmaniasis, Mucocutaneous - genetics Male Leishmaniasis, Cutaneous - immunology Promoter Regions, Genetic - genetics Case-Control Studies Animals Adult Female Polymorphism, Single Nucleotide Leishmaniasis, Cutaneous - genetics Cytokines - immunology

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