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NOD2 and CCDC122-LACC1 genes are associated with leprosy susceptibility in Brazilians |
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| Authors: | Carolinne Sales-Marques Heloisa Salomão Vinicius Medeiros Fava Lucia Elena Alvarado-Arnez Evaldo Pinheiro Amaral Cynthia Chester Cardoso Ida Maria Foschiani Dias-Batista Weber Laurentino da Silva Priscila Medeiros Marcos da Cunha Lopes Virmond Francisco Carlos Félix Lana Antonio Guilherme Pacheco Milton Ozório Moraes Marcelo Távora Mira Ana Carla Pereira Latini |
| Institution: | 1. Laboratório de Hanseníase, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, 21040-360, Brazil 2. Core for Advanced Molecular Investigation, Graduate Program in Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, 80215-901, Brazil 3. Departamento de Enfermagem Materno-Infantil e Saúde Pública, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100, Brazil 4. Departamento de Genética, Laboratório de Virologia Molecular, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-570, Brazil 5. Instituto Lauro de Souza Lima, Rod. Comte. Jo?o Ribeiro de Barros Km 225/226, Aimorés, Bauru, S?o Paulo, CEP 17034-971, 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 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. |
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