IL12B SNPs and copy number variation in IL23R gene associated with susceptibility to leprosy.

Abstract

BACKGROUND:

Genome-wide studies have identified both human leucocyte antigen (HLA) and non-HLA regions in association with leprosy. Involvement of novel functional loci within these regions has been proposed by us earlier.

METHODS:

We investigated the role of 23 single nucleotide polymorphisms (SNPs) in IL12B and IL12RB2 in a total of 2345 individuals from India, using MassArray platform, along with the copy number variations in IL23R, IL12RB2 and IL10 genes in a representative set of 257 individuals, using real-time PCR.

RESULTS:

SNP rs2853694 in IL12B gene (AA vs AC+CC, p=2.6E-04, OR=1.42 (1.17-1.70)) showed an association with leprosy. Pairwise interaction analysis followed by combined analysis of multiple SNPs identified that IL12B, TNF and BTNL2-DRA inter-genic SNPs provided a major risk towards leprosy (p=2.6E-08, OR=3.94 (2.43-6.38)), showing a further increase (p=3.6E-14) for combined risk genotype interactions. On the other hand, IL12B, BAT1, NFKBIL1 and LTA SNPs together showed a disposition towards protection (p=0.000011, OR=0.32 (0.19-0.53)) with a further increase (p=6.38E-10) for combined protective genotype-interactions. Copy number variation analysis showed an increased copy number of the IL23R gene (PB=36.4%, controls=20.2%; p=0.026) associated with the pauci-bacillary form of leprosy, which correlated with a trend towards enhanced expression in memory T cells in a preliminary observation.

CONCLUSIONS:

The observations made here highlight the importance of interaction between specific genetic backgrounds of immune response related genes in the outcome of Mycobacterium leprae infection.

• Authors: Shafat Ali, Amit Kumar Srivastava, Rupali Chopra, Shweta Aggarwal, Vijay Kumar Garg, Sambit Nath Bhattacharya, Rameshwar Nath Koul Bamezai
• Journal: Journal of medical genetics (J Med Genet) Vol. 50 Issue 1 Pg. 34-42 (Jan 2013) ISSN: 1468-6244 [Electronic] England
• PMID: 23240095 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• IL23R protein, human
• Interleukin-12 Subunit p40
• Receptors, Interleukin

Topics

• Adult
• Alleles
• Case-Control Studies
• DNA Copy Number Variations
• Female
• Gene Frequency
• Genetic Predisposition to Disease
• Genotype
• Haplotypes
• Humans
• Interleukin-12 Subunit p40 (genetics)
• Leprosy (genetics)
• Linkage Disequilibrium
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Receptors, Interleukin (genetics)
• Young Adult