01903nas a2200337   4500000000100000008004100001653001200042653002000054653003500074653001100109100002000120700001500140700001200155700002200167700001400189700001400203700002100217700001300238700001500251700002600266700001300292700001400305700001300319700001100332700001300343245009100356300001200447490000800459520108400467022001401551       2014                            d10aleprosy10aGenetic aspects10aNod2 Signaling Adaptor Protein10aBrazil1 aSales-Marques C1 aSalomão H1 aFava VM1 aAlvarado-Arnez LE1 aAmaral EP1 aCardoso C1 aDias-Batista IMF1 aSilva WL1 aMedeiros P1 aCunha Lopes Virmond M1 aLana FCF1 aPacheco A1 aMoraes M1 aMira M1 aLatini A00aNOD2 and CCDC122-LACC1 genes are associated with leprosy susceptibility in Brazilians.  a1525-320 v1333 a<p>Leprosy is a complex disease with phenotypes strongly influenced by genetic variation. A Chinese genome-wide association study (GWAS) depicted novel genes and pathways associated with leprosy susceptibility, only partially replicated by independent studies in different ethnicities. Here, we describe the results of a validation and replication study of the Chinese GWAS in Brazilians, using a stepwise strategy that involved two family-based and three independent case-control samples, resulting in 3,614 individuals enrolled. First, we genotyped a family-based sample for 36 tag single-nucleotide polymorphisms (SNPs) of five genes located in four different candidate loci: CCDC122-LACC1, NOD2, TNFSF15 and RIPK2. Association between leprosy and tag SNPs at NOD2 (rs8057431) and CCDC122-LACC1 (rs4942254) was then replicated in three additional, independent samples (combined ORAA = 0.49, P = 1.39e-06; ORCC = 0.72, P = 0.003, respectively). These results clearly implicate the NOD2 pathway in the regulation of leprosy susceptibility across diverse populations.</p>  a1432-1203