Sales-Marques Carolinne, Salomão Heloisa, Fava Vinicius Medeiros, Alvarado-Arnez Lucia Elena, Amaral Evaldo Pinheiro, Cardoso Cynthia Chester, Dias-Batista Ida Maria Foschiani, da Silva Weber Laurentino, Medeiros Priscila, da Cunha Lopes Virmond Marcos, Lana Francisco Carlos Félix, Pacheco Antonio Guilherme, Moraes Milton Ozório, Mira Marcelo Távora, Pereira Latini Ana Carla
Laboratório de Hanseníase, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, 21040-360, Brazil.
Hum Genet. 2014 Dec;133(12):1525-32. doi: 10.1007/s00439-014-1502-9. Epub 2014 Nov 4.
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.
麻风病是一种复杂的疾病，其表型受到基因变异的强烈影响。一项中国全基因组关联研究（GWAS）描绘了与麻风病易感性相关的新基因和通路，但在不同种族的独立研究中仅部分得到重复验证。在此，我们描述了在巴西人中对中国GWAS进行验证和重复研究的结果，采用了逐步策略，涉及两个基于家系的样本和三个独立的病例对照样本，共纳入3614名个体。首先，我们对一个基于家系的样本进行基因分型，检测位于四个不同候选基因座的五个基因的36个标签单核苷酸多态性（SNP）：CCDC122-LACC1、NOD2、TNFSF15和RIPK2。然后，在另外三个独立样本中重复验证了麻风病与NOD2（rs8057431）和CCDC122-LACC1（rs4942254）标签SNP之间的关联（合并OR(AA)=0.49，P=1.39e-06；OR(CC)=0.72，P=0.003）。这些结果清楚地表明NOD2通路在不同人群中麻风病易感性的调节中起作用。
