Abstract
Aetiology of the establishment of Leishmania donovani infection in its host is still not well understood. Host immune system plays a key role during pathogen entry, survival and propagation of the parasite. Toll-like receptors and its signalling pathways are the hallmarks of the innate immune system and Toll interacting protein (Tollip) is a key regulatory protein of this pathway. Genetic polymorphisms of Tollip gene are known to be associated with a wide range of bacterial and protozoan diseases. However, its role in Visceral Leishmaniasis (VL) as a risk factor is not known. Therefore, we carried out a case-control study to evaluate the role of Tollip gene polymorphism with VL in an endemic population of Assam, India. A total of 206 participants (70 cases and 136 healthy controls) were enrolled in this study. The two Tollip gene polymorphisms rs3750920 and rs5743899 were genotyped by the PCR-RFLP method. The findings show no evidence of deviation from Hardy-Weinberg equilibrium in either of the kala-azar cases or healthy controls. In Tollip variants the rs3750920 &rs5743899 genotype frequency was found within acceptable HWE limits (p-value >0.05). Genetic association of the genotypes of rs3750920 did not show any association with VL. In case of rs5743899, the risk of VL due to allele G was found to be 1.859 times (p-value <0.05) by the recessive model as well as the additive model OR: 1.728 (p-value <0.05). But, the allele G of rs5743899 was indicative of protection against kala-azar in the males as per the multiplicative, co-dominant heterogeneous, recessive as well as the additive model with OR < 1 and p-value <0.05. However, in the males, the allele A of rs5743899 increased the risk factor for kala-azar >2-fold with an OR of 2.228 (p-value <0.05) that is also supported by the additive model OR = 2.07 with a p-value <0.05. The results of this study indicate that the presence of rs5743899 polymorphism may be a risk factor for developing VL even though other alleles confer some degree of protection against VL especially among the male population in this study.
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