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NRAMP1 Polymorphisms like Susceptibility Marker in Mexican Focus of Cutaneous Leishmaniasis
Mirsha Pamela Hernández-Rivera1, Alicia Ramírez-Ramírez2, Adelaido Chiñas-Pérez3
1Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, IPN, Carpio y Plan de Ayala, 11340 Mexico City, Mexico.
Abstract:
Cutaneous leishmaniasis (CL) is endemic in Campeche state, Mexico. Host and parasite factors are involved in the establishment and development of CL. Host factors include immune response and genetic background. NRAMP1 (Natural Resistance Associated Macrophage Protein 1) is important in innate immunity. Polymorphisms in NRAMP1 have been associated with susceptibility or resistance to infectious and autoimmune diseases. To study the association of NRAMP1 mutations with CL in patients from Calakmul, Campeche, samples from 115 CL patients and 69 samples of healthy people from the same area were evaluated. Five regions in NRAMP1 were amplified and digested, looking for mutations in the promoter region (-524G/C), exon 3 (274C/T), exon 8 (823 C7T), and exon 15 (G/A) and deletion of 4 bp in the 3'UTR region. We found a statistical association between polymorphisms in 3'UTR region and exon 8 and CL [χ2 = 13.26; p < 0.05; OR = 17.00; IC of 95% (2.24-128.99)]. Some patients who needed more than 40 doses of Glucantime® to heal injuries presented mutations in exons 3, 8, and 15. Multiple or ear lesions were not associated with NRAMP1 polymorphism.
Insights
Genetic variations in the Natural Resistance Associated Macrophage Protein 1 (NRAMP1) gene are linked to cutaneous leishmaniasis (CL) susceptibility in Mexico. Specific NRAMP1 mutations may influence treatment outcomes for CL patients.
Area of Science:
- Immunogenetics
- Infectious Disease Epidemiology
- Molecular Biology
Background:
- Cutaneous leishmaniasis (CL) is a significant public health concern in Campeche, Mexico.
- Host genetic factors, particularly innate immunity genes like NRAMP1 (Natural Resistance Associated Macrophage Protein 1), play a crucial role in CL pathogenesis.
- NRAMP1 polymorphisms have been implicated in various infectious and autoimmune diseases.
Purpose of the Study:
- To investigate the association between NRAMP1 gene polymorphisms and susceptibility to cutaneous leishmaniasis in a Mexican population.
- To explore potential correlations between NRAMP1 mutations and clinical parameters, including treatment response, in CL patients.
Main Methods:
- Genotyping of 115 CL patients and 69 healthy controls from Calakmul, Campeche, Mexico.
- Analysis of five specific regions within the NRAMP1 gene: promoter (-524G/C), exon 3 (274C/T), exon 8 (823 C7T), exon 15 (G/A), and a 4 bp deletion in the 3'UTR.
- Amplification and digestion techniques were employed to detect NRAMP1 mutations.
Main Results:
- A statistically significant association was found between NRAMP1 polymorphisms in the 3'UTR region and exon 8 and CL susceptibility (χ² = 13.26; p < 0.05; OR = 17.00).
- Patients requiring more than 40 doses of Glucantime® for healing exhibited mutations in exons 3, 8, and 15.
- No association was observed between NRAMP1 polymorphisms and the presence of multiple lesions or ear lesions.
Conclusions:
- NRAMP1 gene variations, specifically in the 3'UTR and exon 8, are associated with cutaneous leishmaniasis in the studied Mexican population.
- Certain NRAMP1 mutations may influence the clinical course and treatment response of CL patients.
- Further research into NRAMP1's role in leishmaniasis pathogenesis is warranted.
