RESUMO
UNLABELLED: Leprosy, a chronic infectious disease caused by Mycobacterium leprae, can damage the peripheral nervous system and represents one of the leading causes of nontraumatic neuropathy in some developing countries. The NINJURIN1 is a cell adhesion molecule that provides suitable substrates for repair of Schwann cells after peripheral nerve injury. The single nucleotide polymorphism NINJ1, is the result of a transversion of an adenine to a nucleotide polymorphic cytokine (AâC), responsible for an amino acid exchange of asparagine to alanine at position 110 of the protein (asp110ala). OBJECTIVES: The aim of this study was to investigate the importance of the polymorphism in the NINJ1 gene for neural impairment during leprosy course. METHODS: A single nucleotide polymorphism (asp110ala) was searched in 218 leprosy patients and 244 non-leprosy subjects using a polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: No statistical differences were observed in the frequency of the asp110ala SNP between leprosy patients versus non-leprosy and multibacillary versus paucibacillary clinical forms. The C allele (ala110) is increased among patients exhibiting nerve impairment (p=0.0379). Also, leprosy patients with the CC genotype (ala/ala) had a higher risk (OR=4.21) of developing nerve disability when compared those carrying the AA genotype (asp/asp) (OR=0.69). CONCLUSION: Our results show an association between the studied C allele (ala110) and damage nerve in leprosy patients. SIGNIFICANCE: Ninjurin analysis showed that asp110ala could be a valuable prognostic marker, since C allele (ala110) have increased susceptibility to nerve damage.
Assuntos
Moléculas de Adesão Celular Neuronais/genética , Hanseníase/patologia , Degeneração Neural/genética , Fatores de Crescimento Neural/genética , Polimorfismo de Nucleotídeo Único , Adenina/metabolismo , Adulto , Idoso , Alanina/genética , Alanina/metabolismo , Alelos , Asparagina/genética , Asparagina/metabolismo , Estudos de Casos e Controles , Moléculas de Adesão Celular Neuronais/metabolismo , Feminino , Genótipo , Humanos , Hanseníase/genética , Hanseníase/microbiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/patogenicidade , Degeneração Neural/microbiologia , Degeneração Neural/patologia , Fatores de Crescimento Neural/metabolismo , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Fatores de RiscoRESUMO
Leprosy is the major cause of non-traumatic neuropathy. Herein, we investigated the role of ninjurin 1, an adhesion molecule involved in nerve regeneration in leprosy. Our results demonstrated that M. leprae stimulates in vitro up-regulation of ninjurin mRNA in cultured Schwann and blood cells as well as in vivo mRNA and protein expression in leprosy nerve biopsies. A polymorphism (asp110ala) was investigated in a case-control study (1123 individuals) and no association was found with leprosy per se or with disseminated forms. Nevertheless, ala110 was associated with functional nerve impairment (OR=2.42; p=0.02 for ala/ala) and with lower mRNA levels. Our data suggests that asp110ala could be a valuable genetic marker of nerve damage in leprosy.