The role of neurotrophin polymorphisms and susceptibility to neural damage in leprosy.

BACKGROUND: Mycobacterium leprae is able to infect Schwann cells leading to neural damage. Neurotrophins are involved in nervous system plasticity and impacts in neural integrity during diseases.

OBJECTIVE: Investigate the association between single nucleotide polymorphisms in neurotrophin genes and leprosy phenotypes, especially neural damage.

DESIGN: We selected SNPs in neurotrophins or its receptors genes associated with neural disorders: rs6265 and rs11030099 of BDNF, rs6330 of BDNF, rs6332 in NT3 and rs2072446 of P75NTR. The association of genetic frequencies with leprosy phenotypes were investigated in a case-control study.

RESULTS: An association of the BDNF SNP rs11030099 with number of affected nerves was demonstrated. The "AA+AC" genotypes demonstrated to be protective against nerve impairment. However, this variation does not affect BDNF serum levels. BDNF is an important factor for myelination of Schwann cells and polymorphisms in this gene can be associated with leprosy outcome. Moreover, rs11030099 is located in the binding region for miRNA 26a that could be involved in control of BDNF expression. We demonstrated different expression levels of this miRNA in polar forms of leprosy.

CONCLUSION: Our findings demonstrate for the first time an association between the polymorphism rs11030099 in the BDNF gene and neural commitment in leprosy and may indicate a possible role of miRNA-26a acting synergistically to these genetic variants in neural damage development.