Abstract
BackgroundVisceral leishmaniasis (VL) is a multifactorial disease, where the host genetics play a significant role in determining the disease outcome. The immunological role of anti-inflammatory cytokine, Interleukin 10 (IL10), has been well-documented in parasite infections and considered as a key regulatory cytokine for VL. Although VL patients in India display high level of IL10 in blood serum, no genetic study has been conducted to assess the VL susceptibility / resistance. Therefore, the aim of this study is to investigate the role of IL10 variations in Indian VL; and to estimate the distribution of disease associated allele in diverse Indian populations.MethodologyAll the exons and exon-intron boundaries of IL10 were sequenced in 184 VL patients along with 172 ethnically matched controls from VL endemic region of India.Result and DiscussionOur analysis revealed four variations; rs1518111 (2195 A>G, intron), rs1554286 (2607 C>T, intron), rs3024496 (4976 T>C, 3’ UTR) and rs3024498 (5311 A>G, 3’ UTR). Of these, a variant g.5311A is significantly associated with VL (χ2=18.87; p =0.00001). In silico approaches have shown that a putative micro RNA binding site (miR-4321) is lost in rs3024498 mRNA. Further, analysis of the above four variations in 1138 individuals from 34 ethnic populations, representing different social and linguistic groups who are inhabited in different geographical regions of India, showed variable frequency. Interestingly, we have found, majority of the tribal populations have low frequency of VL (‘A’ of rs3024498); and high frequency of leprosy (‘T’ of rs1554286), and Behcet’s (‘A’ of rs1518111) associated alleles, whereas these were vice versa in castes. Our findings suggest that majority of tribal populations of India carry the protected / less severe allele against VL, while risk / more severe allele for leprosy and Behcet’s disease. This study has potential implications in counseling and management of VL and other infectious diseases.
Highlights
Visceral leishmaniasis (VL), caused by protozoan parasite Leishmania donovani, is the most severe form of leishmaniasis
Considering the fact that, VL is endemic in Bihar state of India and every Indian population is genetically unique [37], we have aimed to investigate the distribution of risk / protective / severe alleles, observed by the case-control study, among the 34 diverse population of India
Diagnosis of VL was performed at the hospitals by serological and parasitological methods using splenic aspirates accompanied by typical clinical features such as; fever, weight loss, fatigue, anaemia, hepatomegaly, splenomegaly and presence of clinical response to anti-leishmanial treatment [1]
Summary
Visceral leishmaniasis (VL), caused by protozoan parasite Leishmania donovani, is the most severe form of leishmaniasis. Immunological and socio-economical factors play a role in the disease outcome [6,7,8,9]. IL10 cytokine is primarily produced by monocytes and to a lesser extent by lymphocytes; namely type 2 T helper cells (Th2), mastocytes, CD4+CD25+Foxp3+ regulatory T cells, and a certain subset of activated T cells and B cells [10]. It is expressed by different cells of the innate immune system, including dendritic cells (DCs), mast cells, natural killer (NK) cells, eosinophils and neutrophils [11]. The aim of this study is to investigate the role of IL10 variations in Indian VL; and to estimate the distribution of disease associated allele in diverse Indian populations
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