Genetic variations and interactions in anti-inflammatory cytokine pathway genes in the outcome of leprosy: a study conducted on a MassARRAY platform.

Abstract

BACKGROUND:

Mycobacterium leprae is the etiologic pathogen that causes leprosy. The outcome of disease is dependent on the host genetic background.

METHODS:

We investigated the association of 51 single-nucelotide polymorphisms (SNPs) in anti-inflammatory cytokines (IL-10, TGFB1, IL-6, IL-4, and IL-13) and receptors (IL-10RA, IL-10RB, TGFBR1, TGFBR2, IL-6R, IL-4R, IL-5RA, IL-5RB, and IL-13RA1) with susceptibility to leprosy in a case-control study from New Delhi in northern India. This was followed by replication testing of associated SNPs in a geographically distinct and unrelated population from Orissa in eastern India. The functional potential of SNPs was established with in vitro reporter assays.

RESULTS:

Significant associations (P < .05) were observed for 8 polymorphisms (rs1800871, rs1800872, and rs1554286 of IL-10; rs3171425 and rs7281762 of IL-10RB; rs2228048 and rs744751 of TGFBR2; and rs1800797 of IL-6) with leprosy. This association was replicated for 4 SNPs (rs1554286 of IL-10, rs7281762 of IL-10RB, rs2228048 of TGFBR2, and rs1800797 of IL-6). The interaction study revealed a significantly greater association with leprosy risk than was obtained for any SNP individually.

CONCLUSIONS:

This study provides an interesting insight on the cumulative polygenic host component that regulates leprosy pathogenesis.

• Authors: Shweta Aggarwal, Shafat Ali, Rupali Chopra, Amit Srivastava, Ponnusamy Kalaiarasan, Dheeraj Malhotra, Sailesh Gochhait, Vijay K Garg, S N Bhattacharya, Rameshwar N K Bamezai
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 204 Issue 8 Pg. 1264-73 (Oct 15 2011) ISSN: 1537-6613 [Electronic] United States
• PMID: 21917900 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines

Topics

• Case-Control Studies
• Cohort Studies
• Cytokines (genetics, immunology)
• Genetic Predisposition to Disease
• Genetic Variation
• Haplotypes
• Host-Pathogen Interactions
• Humans
• India
• Leprosy (genetics, immunology)
• Linkage Disequilibrium
• Logistic Models
• Mycobacterium leprae (immunology)
• Polymorphism, Single Nucleotide
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization