IL10 variant g.5311A is associated with Visceral Leishmaniasis in Indian population

Background: Visceral 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. Methodology: All 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 Discussion: Our 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

Genotype-Phenotype Study of the Middle Gangetic Plain in India Shows Association of rs2470102 with Skin Pigmentation

Our understanding of the genetics of skin pigmentation has been largely skewed towards populations of European ancestry, imparting less attention to South Asian populations, who behold huge pigmentation diversity. Here, we investigate skin pigmentation variation in a cohort of 1,167 individuals in the Middle Gangetic Plain of the Indian subcontinent. Our data confirm the association of rs1426654 with skin pigmentation among South Asians, consistent with previous studies, and also show association for rs2470102 single nucleotide polymorphism. Our haplotype analyses further help us delineate the haplotype distribution across social categories and skin color. Taken together, our findings suggest that the social structure defined by the caste system in India has a profound influence on the skin pigmentation patterns of the subcontinent. In particular, social category and associated single nucleotide polymorphisms explain about 32% and 6.4%, respectively, of the total phenotypic variance. Phylogeography of the associated single nucleotide polymorphisms studied across 52 diverse populations of the Indian subcontinent shows wide presence of the derived alleles, although their frequencies vary across populations. Our results show that both polymorphisms (rs1426654 and rs2470102) play an important role in the skin pigmentation diversity of South Asians

Sample size, mean age and sex ratio of case and control samples.

<p>Sample size, mean age and sex ratio of case and control samples.</p

Prevalence (yearly in millions) of different infectious disease (Visceral Leishmaniasis, Leprosy, Tuberculosis Malaria and Filaria) in worldwide and Indian region.

<p>Prevalence (yearly in millions) of different infectious disease (Visceral Leishmaniasis, Leprosy, Tuberculosis Malaria and Filaria) in worldwide and Indian region.</p

A. Distribution of genotype frequencies for<i>IL10</i> polymorphism, rs1518111 A>G; rs1554286 C>T; rs3024496 C>T and rs3024498 A>G in VL case and control subjects

<p>. B. Distribution of allele frequencies for <i>IL10</i> polymorphism, rs1518111 A>G; rs1554286 C>T; rs3024496 C>T and rs3024498 A>G in VL case and control subjects.</p

Primer sequence, GC % and annealing temperature of <i>IL10</i> exons.

<p>Primer sequence, GC % and annealing temperature of <i>IL10</i> exons.</p

Linkage Disequilibrium (LD) of studied <i>IL-10</i> loci rs1518111 (2195 A>G, intron), rs1554286 (2607 C>T, intron), rs3024496 (4976 T>C, 3’ UTR), rs3024498 (5311 A>G, 3’ UTR) in VL case and control groups.

<p>Linkage Disequilibrium (LD) of studied <i>IL-10</i> loci rs1518111 (2195 A>G, intron), rs1554286 (2607 C>T, intron), rs3024496 (4976 T>C, 3’ UTR), rs3024498 (5311 A>G, 3’ UTR) in VL case and control groups.</p

The structure of the human <i>IL10</i> (chr1, 206945839–206940947; ENST00000423557).

<p>Exons of the gene are shown in pink, introns in brown. rs1518111 (2195 A>G) and rs1554286 (2607 C>T) were the intronic variant of second and third exons while rs3024496 (4976 T>C) and rs3024498 (5311 A>G) were the 3’ UTR variant of fifth exons.</p

Geographical location and allele distribution of rs1518111 (2195 A>G, intron), rs1554286 (2607 C>T, intron) and rs3024498 (5311 A>G) polymorphism in tribe and caste population of India.

<p>Population no. 1 to 16 belongs to castes (Fig A, C and E). Population no. 17 to 34 belongs to tribes (Fig B, D and F).</p