TY - JOUR
KW - Aged
KW - Case-Control Studies
KW - Female
KW - Gene Regulatory Networks
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - genotype
KW - Humans
KW - Leprosy, Multibacillary
KW - Leprosy, Paucibacillary
KW - Male
KW - Middle Aged
KW - Mycobacterium leprae
KW - Nod2 Signaling Adaptor Protein
KW - Oligonucleotide Array Sequence Analysis
KW - Polymorphism, Single Nucleotide
KW - Signal Transduction
AU - Zhang F
AU - Huang W
AU - Chen S
AU - Sun L
AU - Liu H
AU - Li Y
AU - Cui Y
AU - Yan X
AU - Yang H
AU - Yang R
AU - Chu T
AU - Zhang C
AU - Zhang L
AU - Han J
AU - Yu G
AU - Quan C
AU - Yu Y
AU - Zhang Z
AU - Shi B
AU - Zhang L
AU - Cheng H
AU - Wang C
AU - Lin Y
AU - Zheng H
AU - Fu X
AU - Zuo X
AU - Wang Q
AU - Long H
AU - Sun Y
AU - Cheng Y
AU - Tian H
AU - Zhou F
AU - Liu H
AU - Lu W
AU - He S
AU - Du W
AU - Shen M
AU - Jin Q
AU - Wang Y
AU - Low H
AU - Erwin T
AU - Yang N
AU - Li J
AU - Zhao X
AU - Jiao Y
AU - Mao L
AU - Yin G
AU - Jiang Z
AU - Wang X
AU - Yu J
AU - Hu Z
AU - Gong C
AU - Liu Y
AU - Liu R
AU - Wang D
AU - Wei D
AU - Liu J
AU - Cao W
AU - Cao H
AU - Li Y
AU - Yan W
AU - Wei S
AU - Wang K
AU - Hibberd ML
AU - Yang S
AU - Zhang X
AU - Liu J
AB - <p><b>BACKGROUND: </b>The narrow host range of Mycobacterium leprae and the fact that it is refractory to growth in culture has limited research on and the biologic understanding of leprosy. Host genetic factors are thought to influence susceptibility to infection as well as disease progression.</p><p><b>METHODS: </b>We performed a two-stage genomewide association study by genotyping 706 patients and 1225 controls using the Human610-Quad BeadChip (Illumina). We then tested three independent replication sets for an association between the presence of leprosy and 93 single-nucleotide polymorphisms (SNPs) that were most strongly associated with the disease in the genomewide association study. Together, these replication sets comprised 3254 patients and 5955 controls. We also carried out tests of heterogeneity of the associations (or lack thereof) between these 93 SNPs and disease, stratified according to clinical subtype (multibacillary vs. paucibacillary).</p><p><b>RESULTS: </b>We observed a significant association (P<1.00x10(-10)) between SNPs in the genes CCDC122, C13orf31, NOD2, TNFSF15, HLA-DR, and RIPK2 and a trend toward an association (P=5.10x10(-5)) with a SNP in LRRK2. The associations between the SNPs in C13orf31, LRRK2, NOD2, and RIPK2 and multibacillary leprosy were stronger than the associations between these SNPs and paucibacillary leprosy.</p><p><b>CONCLUSIONS: </b>Variants of genes in the NOD2-mediated signaling pathway (which regulates the innate immune response) are associated with susceptibility to infection with M. leprae.</p>
BT - The New England journal of medicine
C1 - http://www.ncbi.nlm.nih.gov/pubmed/20018961?dopt=Abstract
CN - ZHANG2009
DA - 2009 Dec 31
DO - 10.1056/NEJMoa0903753
IS - 27
J2 - N. Engl. J. Med.
LA - eng
N2 - <p><b>BACKGROUND: </b>The narrow host range of Mycobacterium leprae and the fact that it is refractory to growth in culture has limited research on and the biologic understanding of leprosy. Host genetic factors are thought to influence susceptibility to infection as well as disease progression.</p><p><b>METHODS: </b>We performed a two-stage genomewide association study by genotyping 706 patients and 1225 controls using the Human610-Quad BeadChip (Illumina). We then tested three independent replication sets for an association between the presence of leprosy and 93 single-nucleotide polymorphisms (SNPs) that were most strongly associated with the disease in the genomewide association study. Together, these replication sets comprised 3254 patients and 5955 controls. We also carried out tests of heterogeneity of the associations (or lack thereof) between these 93 SNPs and disease, stratified according to clinical subtype (multibacillary vs. paucibacillary).</p><p><b>RESULTS: </b>We observed a significant association (P<1.00x10(-10)) between SNPs in the genes CCDC122, C13orf31, NOD2, TNFSF15, HLA-DR, and RIPK2 and a trend toward an association (P=5.10x10(-5)) with a SNP in LRRK2. The associations between the SNPs in C13orf31, LRRK2, NOD2, and RIPK2 and multibacillary leprosy were stronger than the associations between these SNPs and paucibacillary leprosy.</p><p><b>CONCLUSIONS: </b>Variants of genes in the NOD2-mediated signaling pathway (which regulates the innate immune response) are associated with susceptibility to infection with M. leprae.</p>
PY - 2009
SP - 2609
EP - 18
T2 - The New England journal of medicine
TI - Genomewide association study of leprosy.
VL - 361
SN - 1533-4406
ER -