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LRRK2 and RIPK2 variants in the NOD 2-mediated signaling pathway are associated with susceptibility to Mycobacterium leprae in Indian populations.
- Source :
-
PloS one [PLoS One] 2013 Aug 28; Vol. 8 (8), pp. e73103. Date of Electronic Publication: 2013 Aug 28 (Print Publication: 2013). - Publication Year :
- 2013
-
Abstract
- In recent years, genome wide association studies have discovered a large number of gene loci that play a functional role in innate and adaptive immune pathways associated with leprosy susceptibility. The immunological control of intracellular bacteria M. leprae is modulated by NOD2-mediated signaling of Th1 responses. In this study, we investigated 211 clinically classified leprosy patients and 230 ethnically matched controls in Indian population by genotyping four variants in NOD2 (rs9302752A/G), LRRK2 (rs1873613A/G), RIPK2 (rs40457A/G and rs42490G/A). The LRRK2 locus is associated with leprosy outcome. The LRRK2 rs1873613A minor allele and respective rs1873613AA genotypes were significantly associated with an increased risk whereas the LRRK2 rs1873613G major allele and rs1873613GG genotypes confer protection in paucibacillary and leprosy patients. The reconstructed GA haplotypes from RIPK2 rs40457A/G and rs42490G/A variants was observed to contribute towards increased risk whereas haplotypes AA was observed to confer protective role. Our results indicate that a possible shared mechanisms underlying the development of these two clinical forms of the disease as hypothesized. Our findings confirm and validates the role of gene variants involved in NOD2-mediated signalling pathways that play a role in immunological control of intracellular bacteria M. leprae.
- Subjects :
- Alleles
Female
Haplotypes genetics
Haplotypes immunology
Humans
India epidemiology
Leprosy epidemiology
Leprosy immunology
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
Male
Nod2 Signaling Adaptor Protein immunology
Polymorphism, Genetic genetics
Polymorphism, Genetic immunology
Protein Serine-Threonine Kinases immunology
Receptor-Interacting Protein Serine-Threonine Kinase 2 immunology
Signal Transduction immunology
Th1 Cells immunology
Genetic Predisposition to Disease
Leprosy genetics
Mycobacterium leprae
Nod2 Signaling Adaptor Protein genetics
Protein Serine-Threonine Kinases genetics
Receptor-Interacting Protein Serine-Threonine Kinase 2 genetics
Signal Transduction genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 24015287
- Full Text :
- https://doi.org/10.1371/journal.pone.0073103