03080nas a2200349 4500000000100000008004100001260001300042653001200055653003000067653001100097653001900108653003800127653001100165653001300176653001200189653002500201653003000226653002600256653004900282653003000331653000900361100001600370700001500386700001300401700001600414245013600430856004100566300001100607490000700618520209100625022001402716 2004 d c2004 Dec10aAlleles10aCation Transport Proteins10aFamily10aGene Frequency10aGenetic Predisposition to Disease10aHumans10aLepromin10aleprosy10aMycobacterium leprae10apolymerase chain reaction10aPolymorphism, Genetic10aPolymorphism, Single-Stranded Conformational10aPromoter Regions, Genetic10aSkin1 aFerreira FR1 aGoulart LR1 aSilva HD1 aGoulart IMB00aSusceptibility to leprosy may be conditioned by an interaction between the NRAMP1 promoter polymorphisms and the lepromin response. uhttp://ila.ilsl.br/pdfs/v72n4a05.pdf a457-670 v723 a
Controversial results have been achieved by attempting to associate the NRAMP1 gene with Mycobacterium leprae susceptibility as well as with the Mitsuda reaction, which represents a specific immune response to M. leprae. This study evaluated this association as well as the interaction of the polymorphism (GT)(n) in the promoter region of the NRAMP1 gene with a specific immune response to M. leprae measured by the intradermal Mitsuda test in leprosy patients and in non-consanguineous household contacts. The study aimed to evaluate the association of this gene polymorphism with resistance or susceptibility to the disease, and/or with clinical forms of the disease, in a population in an endemic area served by the State Reference Center in Sanitary Dermatology and Leprosy, Federal University of Uberlandia, MG, Brazil. Leprosy patients (90) were diagnosed according to Ridley and Jopling criteria and they grouped into multibacillary (MB) and paucibacillary (PB) patients. The control group consisted of 61 non-consanguineous contacts. NRAMP1 promoter genotypes were obtained through amplification by the polymerase chain reaction (PCR) followed by the detection through the low ionic-strength single strand conformational polymorphism (LIS-SSCP) electrophoretic technique. There were no significant differences in the allelic and genotypic frequencies for alleles 2, 3, and 4 in relation to the Mitsuda test among patients and household contacts, nor between those with MB and PB forms. However, individuals with a negative lepromin response associated with genotypes 22 and 23 presented a 7- and 8-fold greater chance of developing leprosy, respectively. Therefore, the NRAMP1 gene promoter polymorphism exhibited an interaction with the lepromin response, suggesting that allele 2 of the NRAMP1 promoter is an independent genetic factor that predisposes cells to enable pathogen survival, probably due to its low efficiency in iron transport. However, establishment of the infection and disease development may be conditioned by other immunological and genetic factors.
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