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.


METHODS
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.


CONCLUSIONS
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.
CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
Anshuman
A
Mishra
CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
Sheikh
S
Nizamuddin
CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
Geethika
G
Arekatla
CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
Satya
S
Prakash
CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
Hemlata
H
Dewangan
CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
Abishai
A
Dominic
Oriental Institute of Science and Technology, Bhopal, India.
Abhishek
A
Mishra
CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
Digumarthi V S
DV
Sudhakar
CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
Narasimha R
NR
Parine
CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
Nitin C
NC
Tupperwar
CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
Kumarasamy
K
Thangaraj
D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D005091:Exons; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D062306:Geography, Medical; D006801:Humans; D007194:India / Q000453:epidemiology; D016753:Interleukin-10 / Q000235:genetics*; D007438:Introns; D007898:Leishmaniasis, Visceral / Q000453:epidemiology / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D017422:Sequence Analysis, DNA; D055815:Young Adult
D016753:Interleukin-10