title: NOD2 and CCDC122-LACC1 genes are associated with leprosy susceptibility in Brazilians.
abstract: 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.
authors.affiliation: Laboratório de Hanseníase, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, 21040-360, Brazil.
authors.forename: Carolinne
authors.initials: C
authors.lastname: Sales-Marques
authors.forename: Heloisa
authors.initials: H
authors.lastname: Salomão
authors.forename: Vinicius Medeiros
authors.initials: VM
authors.lastname: Fava
authors.forename: Lucia Elena
authors.initials: LE
authors.lastname: Alvarado-Arnez
authors.forename: Evaldo Pinheiro
authors.initials: EP
authors.lastname: Amaral
authors.forename: Cynthia Chester
authors.initials: CC
authors.lastname: Cardoso
authors.forename: Ida Maria Foschiani
authors.initials: IM
authors.lastname: Dias-Batista
authors.forename: Weber Laurentino
authors.initials: WL
authors.lastname: da Silva
authors.forename: Priscila
authors.initials: P
authors.lastname: Medeiros
authors.forename: Marcos
authors.initials: M
authors.lastname: da Cunha Lopes Virmond
authors.forename: Francisco Carlos Félix
authors.initials: FC
authors.lastname: Lana
authors.forename: Antonio Guilherme
authors.initials: AG
authors.lastname: Pacheco
authors.forename: Milton Ozório
authors.initials: MO
authors.lastname: Moraes
authors.forename: Marcelo Távora
authors.initials: MT
authors.lastname: Mira
authors.forename: Ana Carla
authors.initials: AC
authors.lastname: Pereira Latini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001938:Brazil; D002648:Child; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007918:Leprosy / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein