02714nas a2200325   4500000000100000008004100001653002500042653001300067653002300080653002100103653002000124653001200144653000900156653000800165653002400173100002400197700001400221700002200235700001800257700001900275700002000294700001500314700001300329700002100342245022400363300001200587490000700599520176800606022001402374       2018                            d10aAllelic transmission10aColombia10aGene polymorphisms10aGenetic variants10aImmune response10aleprosy10aMBL210aMPZ10aMyelin Protein Zero1 aCardona-Pemberthy V1 aRendón M1 aCamilo Beltrán J1 aSoto-Ospina A1 aMuñoz-Gomez A1 aAraque-Marín P1 aCorredor M1 aBedoya G1 aCardona-Castro N00aGenetic variants, structural, and functional changes of Myelin Protein Zero and Mannose-Binding Lectin 2 protein involved in immune response and its allelic transmission in families of patients with leprosy in Colombia.  a215-2230 v613 a<p>Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Genetic factors associated with immune response contribute to infection development and disease. M. leprae has the capacity to invade Schwann cells in the peripheral nervous system and cause neuropathy. However, while the responsible molecular mechanisms remain to be fully unveiled, they have begun being elucidated. We studied genetic variants Myelin Protein Zero (MPZ), a major structural component of the myelin sheath, and Mannose Binding Lectin 2 (MBL2), a protein involved in immune response, in 112 family groups of 114 leprosy patients using PCR-RFLP, aiming to calculate the association and allelic transmission of variants associated in first, second and third-degree relatives. Polymorphisms found in MPZ and MBL2 showed association with leprosy. Different probabilities for allelic transmission were found for first and second-degree relatives, a fact that is important to take into account when evaluating risk in contacts of leprosy patients. Structural analysis allows the study of putative amino acids and their possible effect on protein structure and function, as well as on the assembly of a protein homotetramer. Our results suggest that the identified MPZ and MBL2 gene mutations are associated with leprosy in a Colombian population, which correlates with MPZ and MBL2 protein function, and increase the risk of M. leprae infection in leprosy-patients' family members. Additionally, structural analyses were carried out specifically for MPZ protein using information available in databases, and analyzing the substitutions in wildtype and mutant protein. The results show significant structural changes, which may be associated to infection and pathogenicity.</p>
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