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

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.

SUBMITTER: Ramasawmy R

PROVIDER: S-EPMC2878927 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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

Ramasawmy Rajendranath R 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

Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 20100427 5

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 contr ...[more]

PMID: 20430117

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Project description:BackgroundCutaneous leishmaniasis (CL) is a vector-borne disease classified by the World Health Organization as one of the most neglected tropical diseases. Brazil has the highest incidence of CL in America and is one of the ten countries in the world with the highest number of cases. Understanding the spatiotemporal dynamics of CL is essential to provide guidelines for public health policies in Brazil. In the present study we used a spatial and temporal statistical approach to evaluate the dynamics of CL in Brazil.MethodsWe used data of cutaneous leishmaniasis cases provided by the Ministry of Health of Brazil from 2001 to 2017. We calculated incidence rates and used the Mann-Kendall trend test to evaluate the temporal trend of CL in each municipality. In addition, we used Kuldorff scan method to identify spatiotemporal clusters and emerging hotspots test to evaluate hotspot areas and their temporal trends.ResultsWe found a general decrease in the number of CL cases in Brazil (from 15.3 to 8.4 cases per 100 000 habitants), although 3.2% of municipalities still have an increasing tendency of CL incidence and 72.5% showed no tendency at all. The scan analysis identified a primary cluster in northern and central regions and 21 secondary clusters located mainly in south and southeast regions. The emerging hotspots analysis detected a high spatial and temporal variability of hotspots inside the main cluster area, diminishing hotspots in eastern Amazon and permanent, emerging, and new hotspots in the states of Amapá and parts of Pará, Roraima, Acre and Mato Grosso. The central coast the state of Bahia is one of the most critical areas due to the detection of a cluster of the highest rank in a secondary cluster, and because it is the only area identified as an intensifying hotspot.ConclusionsUsing a combination of statistical methods we were able to detect areas of higher incidence of CL and understand how it changed over time. We suggest that these areas, especially those identified as permanent, new, emerging and intensifying hotspots, should be targeted for future research, surveillance, and implementation of vector control measures.

Dataset Information

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

Publications

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

Similar Datasets

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