title: LRRK2 and RIPK2 variants in the NOD 2-mediated signaling pathway are associated with susceptibility to Mycobacterium leprae in Indian populations.
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.
authors.affiliation: Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcinek
authors.forename: Aditya Nath
authors.initials: AN
authors.lastname: Jha
authors.forename: Vidyagouri
authors.initials: V
authors.lastname: Shinde
authors.forename: Arun
authors.initials: A
authors.lastname: Sundaramoorthy
authors.forename: Raja
authors.initials: R
authors.lastname: Rajkumar
authors.forename: Naveen Chandra
authors.initials: NC
authors.lastname: Suryadevara
authors.forename: Sanjeev Kumar
authors.initials: SK
authors.lastname: Neela
authors.forename: Hoang
authors.initials: H
authors.lastname: van Tong
authors.forename: Vellingiri
authors.initials: V
authors.lastname: Balachander
authors.forename: Vijaya Lakshmi
authors.initials: VL
authors.lastname: Valluri
authors.forename: Kumarasamy
authors.initials: K
authors.lastname: Thangaraj
authors.forename: Thirumalaisamy P
authors.initials: TP
authors.lastname: Velavan
mesh_terms: D000483:Alleles; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics / Q000276:immunology; D006801:Humans; D007194:India / Q000453:epidemiology; D007918:Leprosy / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D009166:Mycobacterium leprae; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000276:immunology; D011110:Polymorphism, Genetic / Q000235:genetics / Q000276:immunology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000276:immunology; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2 / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics* / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; C506253:RIPK2 protein, human; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2