Análise da influência de polimorfismo do gene TLR1 na suscetibilidade à hanseníase per se: um estudo de caso-controle

Abstract

Since the 60s, there is evidence of the genetic architecture influence in susceptibility to leprosy. Polymorphisms in genes encoding cytokines and receptors involved in immune response, such as TLR1 receptor that can recognize the pathogen, may be associated with the risk of disease. The objective of this study was to analyze the influence of the G743Apolymorphism in the TLR1 gene with susceptibility to leprosy in a case-control study in the micro-region of Almenara, Minas Gerais. The scenario involved the cities of Almenara, Felisburgo, Jacinto, Jordânia, Palmópolis and Rubim. The case sample was selected in consultation with individuals diagnosed with leprosy registered in SINAN between 2001 and 2014. Controls were selected from the household contacts of these cases. Including those who lived in the selected cities, age greater than or equal seven years old and who accepted the biological material collection. Contacts with a history or suspected leprosy and onsanguinitywith cases were excluded. Data collection involved home visits with a structured questionnaire and blood collection, carried out in 2011 and 2014. The DNA extraction used the Qiagen kit Flexigene and genotyping performed by Real-Time PCR. The Epi Info software was used to build the database and the analysis done in SPSS software and R withthe SNPassoc statistical package. This study was approved by the Ethics Committee of the Federal University of Minas Gerais. A sample of 234 cases and 233 controls amounted to 467 individuals, most adult females. Only between cases predominated males and a higherproportion of young people. In epidemiological variables, there was a significant number of individuals living in houses with up to 4 rooms and helminths history, especially among the cases. The multibacillary form was common in the case group as well as physical disabilities,leprosy reactions and the absence of BCG vaccination scar. Among controls, many lived with more than one case of leprosy in intradomiciliary environments and for long periods. The association analysis of G743A polymorphism with leprosy revealed higher frequency of the743A allele between cases, but the genotypes analysis did not found statistically significant result of 743AA with susceptibility to leprosy per se, however, the heterozygous genotype 743GA was associated with protection in women, suggesting that the G743A polymorphismis a gender-specific protection factor for leprosy. New genetic epidemiology studies using other genes involved in the immune response and a greater number of polymorphisms are needed so that one can clarify the genetic profile of susceptibility to leprosy.