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The -2518bp promoter polymorphism at CCL2/MCP1 influences susceptibility to mucosal but not localized cutaneous leishmaniasis in Brazil.
- Source :
-
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases [Infect Genet Evol] 2010 Jul; Vol. 10 (5), pp. 607-13. Date of Electronic Publication: 2010 Apr 27. - Publication Year :
- 2010
-
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.<br /> (Copyright 2010 Elsevier B.V. All rights reserved.)
- Subjects :
- Adult
Animals
Brazil
Case-Control Studies
Cytokines immunology
Female
Gene Frequency
Genetic Association Studies
Genotype
Humans
Leishmaniasis, Cutaneous immunology
Leishmaniasis, Mucocutaneous immunology
Male
Middle Aged
Chemokine CCL2 genetics
Genetic Predisposition to Disease
Leishmania braziliensis
Leishmaniasis, Cutaneous genetics
Leishmaniasis, Mucocutaneous genetics
Polymorphism, Single Nucleotide
Promoter Regions, Genetic genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1567-7257
- Volume :
- 10
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases
- Publication Type :
- Academic Journal
- Accession number :
- 20430117
- Full Text :
- https://doi.org/10.1016/j.meegid.2010.04.006