Polymorphism in Toll interacting protein (TOLLIP) gene and its association with Visceral Leishmaniasis

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.