1. NOD2 and CCDC122-LACC1 genes are associated with leprosy susceptibility in Brazilians
- Author
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Ida Maria Foschiani Dias-Batista, Marcelo Távora Mira, Francisco Carlos Félix Lana, Vinicius M. Fava, Lucia Elena Alvarado-Arnez, Heloisa Salomão, Priscila Medeiros, Evaldo Pinheiro Amaral, Ana Carla Pereira Latini, Cynthia Chester Cardoso, Weber Laurentino da Silva, Carolinne Sales-Marques, Marcos Virmond, Antonio G. Pacheco, and Milton Ozório Moraes
- Subjects
Adult ,Male ,Linkage disequilibrium ,Adolescent ,Nod2 Signaling Adaptor Protein ,Single-nucleotide polymorphism ,Genome-wide association study ,Biology ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,Young Adult ,Gene Frequency ,Leprosy ,Genetic variation ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Child ,Allele frequency ,Genetic Association Studies ,Genetics (clinical) ,Aged ,Middle Aged ,medicine.disease ,Phenotype ,Human genetics ,Female ,Brazil - 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.
- Published
- 2014