TY - JOUR
T1 - IL10 variant g.5311A is associated with visceral leishmaniasis in Indian population
AU - Mishra, Anshuman
AU - Nizamuddin, Sheikh
AU - Arekatla, Geethika
AU - Prakash, Satya
AU - Dewangan, Hemlata
AU - Dominic, Abishai
AU - Mishra, Abhishek
AU - Sudhakar, Digumarthi V.S.
AU - Parine, Narasimha R.
AU - Tupperwar, Nitin C.
AU - Thangaraj, Kumarasamy
N1 - Funding Information:
AM was supported by DBT-RA programme (Fellowship) and travel grant of Indian Council of Medical Research and Immunology foundation; SN was supported by ICMR-SRF programme; KT was supported by CSIR Network project (Genesis-BSC0121) and BBSRC, UK (BB/H009337); We acknowledge the help of Dr. B.N. Jha (District Hospital, Muzaffarpur), Dr. Gyan Bhusan (CMO, Muzaffarpur), Dr. T. Prashant Nikhil, Mr. Jitendra kumar and the subjects, who have voluntarily participated in this study.
Publisher Copyright:
© 2015 Mishra et al.
PY - 2015/5/5
Y1 - 2015/5/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84929120186&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0124559
DO - 10.1371/journal.pone.0124559
M3 - Article
C2 - 25941808
AN - SCOPUS:84929120186
VL - 10
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 5
M1 - e0124559
ER -
