03244nas a2200349   4500000000100000008004100001260001200042653002900054653003600083653001200119653001500131653001600146100001900162700001200181700001600193700002300209700001600232700001600248700001200264700001600276700001500292700001400307700002400321700001300345700002400358245013300382856008000515300001100595490000600606520226800612022001402880       2021                            d  c01/202110aToll-like receptor (TLR)10aErythema nodosum leprosum (ENL)10aleprosy10aPrednisone10aThalidomide1 aMaciel-Fiuza M1 aCosta P1 aKowalski TW1 aSchüler-Faccini L1 aBonamigo RR1 aVetoratto R1 aEidt LM1 ade Moraes P1 aSilveira M1 aCamargo L1 aCallegari-Jacques S1 aCastro S1 aSales Luiz Vianna F00aEvaluation of Polymorphisms in Toll-Like Receptor Genes as Biomarkers of the Response to Treatment of Erythema Nodosum Leprosum.  uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8819000/pdf/fmed-08-713143.pdf  a7131430 v83 a<p>Erythema nodosum leprosum (ENL) is an inflammatory complication caused by a dysregulated immune response to . Some Toll-like receptors (TLRs) have been identified as capable of recognizing antigens from , triggering a wide antimicrobial and inflammatory response. Genetic polymorphisms in these receptors could influence in the appearance of ENL as well as in its treatment. Thus, the objective of this work was to evaluate the association of genetic variants of genes with the response to treatment of ENL with thalidomide and prednisone. A total of 162 ENL patients were recruited from different regions of Brazil and clinical information was collected from their medical records. Genomic DNA was isolated from blood and saliva samples and genetic variants in (rs4833095), (rs3804099), (rs1927914), and (rs5743810) genes were genotyped by TaqMan real-time PCR system. In order to evaluate the variants' association with the dose of the medications used during the treatment, we applied the Generalized Estimating Equations (GEE) analysis. In the present sample, 123 (75.9%) patients were men and 86 (53.1%) were in treatment for leprosy during the ENL episode. We found an association between polymorphisms in /rs4833095, /rs3804099, /rs1927914, and /rs5783810 with the dose variation of thalidomide in a time-dependent manner, i.e., the association with the genetic variant and the dose of the drug was different depending on the moment of the treatment evaluated. In addition, we identified that the association of polymorphisms in /rs4833095, /rs3804099, and /rs5783810 with the dose variation of prednisone also were time-dependent. Despite these associations, in all the interactions found, the influence of genetic variants on dose variation was not clinically relevant for therapeutic changes. The results obtained in this study show that TLRs polymorphism might play a role in the response to ENL treatment, however, in this context, they could not be considered as useful biomarkers in the clinical setting due small differences in medication doses. A larger sample size with patients with a more genetic profile is fundamental in order to estimate the association of genetic variants with the treatment of ENL and their clinical significance.</p>
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