02303nas a2200337   4500000000100000008004100001653001900042653001000061653002500071653001000096653001200106653001000118100001500128700001000143700001200153700002100165700001500186700001900201700001300220700001100233700001800244700001400262700001600276700001500292245015000307856007700457300001100534490000600545050001900551520139500570       2013                            d10aSusceptibility10aRIPK210aMycobacterium leprae10aLRRK210aleprosy10aIndia1 aMarcinek P1 aJha A1 aShinde 1 aSundaramoorthy A1 aRajkumar R1 aSuryadevara NC1 aNeela SK1 aTong H1 aBalachander V1 aValluri V1 aThangaraj K1 aVelavan TP00aLRRK2 and RIPK2 variants in the NOD 2-mediated signaling pathway are associated with susceptibility to mycobacterium leprae in Indian populations  uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756038/pdf/pone.0073103.pdf  ae731030 v8  aMARCINECK 20133 aIn 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.