|Title||NOD2 and CCDC122-LACC1 genes are associated with leprosy susceptibility in Brazilians.|
|Publication Type||Journal Article|
|Authors||Sales-Marques C, Salomão H, Fava VM, Alvarado-Arnez LE, Amaral EP, Cardoso CC, Dias-Batista IMF, da Silva WL, Medeiros P, da Cunha Lopes Virmond M, Lana FCF, Pacheco AG, Moraes MO, Mira MT, Pereira Latini AC|
|Abbrev. Journal||Hum. Genet.|
|Year of Publication||2014|
|Keywords||Brazil, Genetic aspects, Leprosy, Nod2 Signaling Adaptor Protein|
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.