Association of NRAMP1 polymorphism with leprosy type but not susceptibility to leprosy per se in west Africans
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DNA Fingerprinting of Mycobacterium leprae Strains Using Variable Number Tandem Repeat (VNTR) - Fragment Length Analysis (FLA)
Published on: July 15, 2011
S J Meisner1, S Mucklow, G Warner
1Wellcome Trust Centre for Human Genetics, University of Oxford, United Kingdom.
Abstract:
Twin and family studies indicate that host genetic factors influence susceptibility to leprosy and, possibly, leprosy type. Murine studies have suggested a role for the natural resistance-associated macrophage protein 1 (Nramp1) gene, which can influence cellular immune responses to intracellular pathogens. We evaluated a variation in the human homolog, NRAMP1, recently associated with tuberculosis susceptibility in West Africa. A total of 273 patients with leprosy and 201 controls from Mali were genotyped for NRAMP1 polymorphisms previously associated with tuberculosis. No association was found with leprosy per se (P = 0.83), but the NRAMP1 3'-untranslated region 4-bp insertion/deletion polymorphism was associated with leprosy type (P = 0.007). Heterozygotes were more frequent among multibacillary than paucibacillary leprosy cases. Thus, variation in or near the NRAMP1 gene may exert an influence on the clinical presentation of leprosy, possibly by influencing cellular immune response type.
Insights
Genetic variations in the natural resistance-associated macrophage protein 1 (NRAMP1) gene influence leprosy type, not overall susceptibility. Heterozygotes for NRAMP1 polymorphisms were more common in multibacillary leprosy patients.
Area of Science:
- Genetics
- Immunology
- Infectious Diseases
Background:
- Host genetic factors significantly impact leprosy susceptibility and disease classification.
- The natural resistance-associated macrophage protein 1 (Nramp1) gene plays a role in cellular immunity against intracellular pathogens.
- Previous research linked NRAMP1 variations to tuberculosis susceptibility in West Africa.
Purpose of the Study:
- To investigate the association between NRAMP1 gene polymorphisms and leprosy in a West African population.
- To determine if NRAMP1 variations influence leprosy susceptibility or disease type.
Main Methods:
- Genotyping of NRAMP1 polymorphisms in 273 leprosy patients and 201 controls from Mali.
- Statistical analysis to assess the association between NRAMP1 variations and leprosy per se, and leprosy classification (paucibacillary vs. multibacillary).
Main Results:
- No significant association was found between NRAMP1 polymorphisms and overall leprosy susceptibility (P = 0.83).
- A significant association (P = 0.007) was observed between the NRAMP1 3'-untranslated region 4-bp insertion/deletion polymorphism and leprosy type.
- Individuals with multibacillary leprosy showed a higher frequency of NRAMP1 heterozygosity compared to those with paucibacillary leprosy.
Conclusions:
- Variations in or near the NRAMP1 gene may influence the clinical presentation of leprosy.
- The NRAMP1 gene's role in cellular immune responses could affect the type of leprosy developed.
- NRAMP1 polymorphisms are associated with leprosy classification, suggesting a role in disease manifestation rather than initial susceptibility.
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