IL10 Variant g.5311A Is Associated with Visceral Leishmaniasis in Indian Population

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.

Influence of genetic variants of gamma interferon, interleukins 10 and 12 on Visceral Leishmaniasis in an endemic area, Iran

“…In agreement with our results, Hajilooi et al reported that the distributions of alleles A and G at position −1082 and alleles C and T at position −819 of IL-10 gene were comparable between VL patients and controls but they showed that AG and CT genotypes at position −1082 and −819, respectively, were more frequent in patients than in controls [3]. Moreover, Mishra et al reported a variant of IL-10 (g.5311A) which was significantly associated with VL in a region of India [19]. Although IL-10 is known as an anti-inflammatory cytokine and its upregulated level has been reported in different studies during the acute phase of VL [20,21], the discrepancies between different studies from different areas of the worlds may imply that IL-10 SNPs could not explain simply its role in the VL pathogenesis and other cytokines corresponding to both innate and acquired immune responses may be involved.…”

Association between interleukin 10 (IL-10) polymorphisms and leishmaniasis progression: a systematic review and meta-analysis

“…Both Hajilooi et al 25 , 30 studies demonstrated SNP influence in the progression of VL, particularly, rs1800871 and 1800896 IL-10 SNPs, respectively. Mishra et al 29 demonstrated that of the four SNPs analysed, only rs3024498 showed association with VL. However, Shehadeh et al 27 presented no association of IL-10 polymorphisms and VL progression, neither with rs1800871 nor rs1800896.…”

“…Despite the evidence of the role of IL-10 in the persistence of leishmaniasis regardless of immune response, our findings demonstrate no significant association between rs1800871 and rs1800896 and the progression of leishmaniasis. Nevertheless, future research on the subject with greater methodological rigor and sample sizes is mandatory to clarify the role of IL-10 and its genetic profiles on disease progression and treatment 26 , 29 .…”

Skin Pigmentation Diversity in Central East Indian Populations and its Correlation with Mitochondrial Haplogroups

“…Phenotype diversity, unlimited human migrations, existence of various endemic regions, foci of various infectious disease and diversified population makes the importance of this type of study in India [9,20]. The modern human habitations in central east regions were during Paleolithic times.…”