NOD2 and CCDC122-LACC1 genes are associated with leprosy susceptibility in Brazilians

• DOI: 10.1007/s00439-014-1502-9
• Publication Date: 2014-11-03T02:31:51Z
• Authors: Carolinne Sales-M...; Heloisa Salomão; Vinicius Medeiros...; Lucia Elena Alvar...; Evaldo Pinheiro A...; Cynthia Chester C...; Ida Maria Foschia...; Weber Laurentino ...; Priscila Medeiros; Marcos da Cunha L...; Francisco Carlos ...; Antonio Guilherme...; Milton Ozório Moraes; Marcelo Távora Mira; Ana Carla Pereira...
• Keywords: Adult; Male; 0301 basic medicine; Adolescent; Nod2 Signaling Adaptor Protein; Middle Aged; Polymorphism, Single Nucleotide; Linkage Disequilibrium; 3. Good health; Young Adult; 03 medical and health sciences; Gene Frequency; Leprosy; Humans; Female; Genetic Predisposition to Disease; Child; Brazil; Genetic Association Studies; Aged

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 OR(AA) = 0.49, P = 1.39e-06; OR(CC) = 0.72, P = 0.003, respectively). These results clearly implicate the NOD2 pathway in the regulation of leprosy susceptibility across diverse populations.