TY - JOUR
KW - leprosy
KW - Genetic aspects
KW - Nod2 Signaling Adaptor Protein
KW - Brazil
AU - Sales-Marques C
AU - Salomão H
AU - Fava VM
AU - Alvarado-Arnez LE
AU - Amaral EP
AU - Cardoso C
AU - Dias-Batista IMF
AU - Silva WL
AU - Medeiros P
AU - Cunha Lopes Virmond M
AU - Lana FCF
AU - Pacheco A
AU - Moraes M
AU - Mira M
AU - Latini A
AB - <p>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.</p>
BT - Human genetics
C1 - http://www.ncbi.nlm.nih.gov/pubmed/25367361?dopt=Abstract
DO - 10.1007/s00439-014-1502-9
IS - 12
J2 - Hum. Genet.
LA - eng
N2 - <p>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.</p>
PY - 2014
SP - 1525
EP - 32
T2 - Human genetics
TI - NOD2 and CCDC122-LACC1 genes are associated with leprosy susceptibility in Brazilians.
VL - 133
SN - 1432-1203
ER -