Polymorphism of human NRAMP1 gene, levels of anti-PGL-1 antibodies and susceptibility to leprosy in endemic areas of Pará State, Brazil

Abstract

The human gene of natural resistance which encodes a protein detected in macrophage - NRAMP1 seems to be involved in the influence on the pattern of immune response to infection by Mycobacterium leprae. It was evaluated the association of the polymorphism of this gene (3'UTR ins/del CAAA) in leprosy per se with types of that disease, also related to the levels of anti-PGL-1 antibodies, representing the pattern of humoral immune response (TH2 type) in this population. A total of 122 leprosy patients and 110 non-patients, coming from endemic municipalities in Pará State, Brazil, were genotyped for this polymorphism and analyzed according to the levels of anti-PGL-1 antibodies of this mycobacterium. An association was observed in leprosy per se (p = 0.0087), and polymorphism of the 3' untranslated region of the NRAMP1 gene with insertion/deletion of four base pairs (CAAA) was strongly associated with the multibacillary form (p = 0.025) compared to the non-consanguineous group of contact. Heterozygous and allele carriers with deletion (159 bp) were more frequent among multibacillary than in the paucibacillary forms. The haplotypes of NRAMP1 gene, in this study, have an important influence on clinical presentation of leprosy, also determined by the positivity to PGL-1 antigen of M. leprae, expression of humoral immune response in leprosy.