Human Genetics

, Volume 131, Issue 5, pp 703–716

Association of variants in BAT1-LTA-TNF-BTNL2 genes within 6p21.3 region show graded risk to leprosy in unrelated cohorts of Indian population

  • Shafat Ali
  • Rupali Chopra
  • Shweta Aggarwal
  • Amit Kumar Srivastava
  • Ponnusamy Kalaiarasan
  • Dheeraj Malhotra
  • Sailesh Gochhait
  • Vijay K. Garg
  • S. N. Bhattacharya
  • Rameshwar N. K. Bamezai
Original Investigation

DOI: 10.1007/s00439-011-1114-6

Cite this article as:
Ali, S., Chopra, R., Aggarwal, S. et al. Hum Genet (2012) 131: 703. doi:10.1007/s00439-011-1114-6

Abstract

Host immune response against Mycobacterium leprae plays an important role in providing resistance to infection and disease progression. Genome-wide linkage and association studies suggest the possibility of multiple risk loci within HLA (6p21.3) region. Any systematic study of relevance within the histocompatibility complex of importance in host immune response would be pertinent because of non-replication of the known loci and unavailable information on some of the unexplored genes and regions. A systematic scan was performed of the selected region involving LTA-TNF-LTB genes within 6p21.3 with a resolution of 1SNP/127 bp; and the SNPs in flanking BAT1, NFKBIL and BTNL2-DRA genes on the basis of their tag status or their presence in promoter/exonic regions with MAF of >5%. Nine SNPs located in BAT1, LTA, TNF genes and BTNL2-DRA interval showed strong association with leprosy susceptibility in two independent sets of North Indian population which was replicated in a geographically distinct East Indian population. Conditional logistic regression showed at least one functional SNP remaining significant in each gene, suggesting an independent role of each of the disease associated SNPs. In vitro reporter assay revealed that two SNPs located at BAT1 promoter and 13 kb upstream to LTA gene affected the transcription factor binding site, hence the gene expression. We unravel the role of unexplored immunologically important genes, BAT1 and BTNL2, in addition to known LTA and TNF genes, and the haplotypes of the significantly associated SNPs therein, to understand susceptibility to the disease, leprosy and its differential severity.

Supplementary material

439_2011_1114_MOESM1_ESM.doc (602 kb)
Supplementary material 1 (DOC 602 kb)

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Shafat Ali
    • 1
  • Rupali Chopra
    • 1
  • Shweta Aggarwal
    • 1
  • Amit Kumar Srivastava
    • 1
  • Ponnusamy Kalaiarasan
    • 1
  • Dheeraj Malhotra
    • 1
  • Sailesh Gochhait
    • 1
  • Vijay K. Garg
    • 2
  • S. N. Bhattacharya
    • 3
  • Rameshwar N. K. Bamezai
    • 1
    • 4
  1. 1.National Centre of Applied Human Genetics, School of Life SciencesJawaharlal Nehru UniversityNew DelhiIndia
  2. 2.Department of Dermatology and Sexually Transmitted Diseases, Maulana Azad Medical CollegeLok Nayak Jai Prakash HospitalNew DelhiIndia
  3. 3.Department of Dermatology and VenereologyUniversity College of Medical Sciences and GTB HospitalDelhiIndia
  4. 4.SMVDUKatra, JammuIndia