The -2518bp promoter polymorphism at CCL2/MCP1 influences susceptibility to mucosal but not localized cutaneous leishmaniasis in Brazil.
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.
Ramasawmy
Rajendranath
R
Universidade Federal da Bahia, Salvador, Brazil.
Menezes
Eliane
E
Magalhães
Andrea
A
Oliveira
Joyce
J
Castellucci
Léa
L
Almeida
Roque
R
Rosa
Maria Elisa A
ME
Guimarães
Luiz Henrique
LH
Lessa
Marcus
M
Noronha
Elza
E
Wilson
Mary E
ME
Jamieson
Sarra E
SE
Kalil
Jorge
J
Blackwell
Jenefer M
JM
Carvalho
Edgar M
EM
de Jesus
Amélia Ribeiro
AR
D000328:Adult; D000818:Animals; D001938:Brazil; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000235:genetics*; D016207:Cytokines / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007892:Leishmania braziliensis; D016773:Leishmaniasis, Cutaneous / Q000235:genetics* / Q000276:immunology; D007897:Leishmaniasis, Mucocutaneous / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*
D018932:Chemokine CCL2; D016207:Cytokines