Genomewide Association Study of Leprosy

被引：573

作者：

Zhang, Fu-Ren ^{[1
]}

Huang, Wei ^{[1
]}

Chen, Shu-Min ^{[1
]}

Sun, Liang-Dan ^{[1
]}

Liu, Hong ^{[1
]}

Li, Yi ^{[1
]}

Cui, Yong ^{[1
]}

Yan, Xiao-Xiao ^{[1
]}

Yang, Hai-Tao ^{[1
]}

Yang, Rong-De ^{[1
]}

Chu, Tong-Sheng ^{[1
]}

Zhang, Chi ^{[1
]}

Zhang, Lin ^{[1
]}

Han, Jian-Wen ^{[1
]}

Yu, Gong-Qi ^{[1
]}

Quan, Cheng ^{[1
]}

Yu, Yong-Xiang ^{[1
]}

Zhang, Zheng ^{[1
]}

Shi, Ben-Qing ^{[1
]}

Zhang, Lian-Hua ^{[1
]}

Cheng, Hui ^{[1
]}

Wang, Chang-Yuan ^{[1
]}

Lin, Yan ^{[1
]}

Zheng, Hou-Feng ^{[1
]}

Fu, Xi-An ^{[1
]}

Zuo, Xian-Bo ^{[1
]}

Wang, Qiang ^{[1
]}

Long, Heng ^{[1
]}

Sun, Yi-Ping ^{[1
]}

Cheng, Yi-Lin ^{[1
]}

Tian, Hong-Qing ^{[1
]}

Zhou, Fu-Sheng ^{[1
]}

Liu, Hua-Xu ^{[1
]}

Lu, Wen-Sheng ^{[1
]}

He, Su-Min ^{[1
]}

Du, Wen-Li ^{[1
]}

Shen, Min ^{[1
]}

Jin, Qi-Yi ^{[1
]}

Wang, Ying ^{[1
]}

Low, Hui-Qi ^{[1
]}

Erwin, Tantoso ^{[1
]}

Yang, Ning-Han ^{[1
]}

Li, Jin-Yong ^{[1
]}

Zhao, Xin ^{[1
]}

Jiao, Yue-Lin ^{[1
]}

Mao, Li-Guo ^{[1
]}

Yin, Gang ^{[1
]}

Jiang, Zhen-Xia ^{[1
]}

Wang, Xiao-Dong ^{[1
]}

Yu, Jing-Ping ^{[1
]}

机构：

[1] Shandong Acad Med Sci, Shandong Prov Inst Dermatol & Venereol, Jinan 250022, Shandong, Peoples R China

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2009年 / 361卷 / 27期

关键词：

INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; SUSCEPTIBILITY; IMMUNITY; MYCOBACTERIA; GENETICS; GENES; HLA;

D O I：

10.1056/NEJMoa0903753

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND 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. METHODS 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). RESULTS 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. CONCLUSIONS Variants of genes in the NOD2-mediated signaling pathway ( which regulates the innate immune response) are associated with susceptibility to infection with M. leprae.

引用

页码：2609 / 2618

页数：10

共 38 条

[1] ABEL L, 1988, AM J HUM GENET, V42, P256
[2] COMPLEX SEGREGATION ANALYSIS OF LEPROSY IN SOUTHERN VIETNAM
ABEL, L
LAP, VD
OBERTI, J
VANTHUC, N
VANCUA, V
GUILLOUDBATAILLE, M
SCHURR, E
LAGRANGE, PH
[J]. GENETIC EPIDEMIOLOGY, 1995, 12 (01) : 63 - 82
[3] Stepwise replication identifies a low-producing lymphotoxin-α allele as a major risk factor for early-onset leprosy
Alcais, Alexandre
Alter, Andrea
Antoni, Guillemette
Orlova, Marianna
Van Thuc, Nguyen
Singh, Meenakshi
Vanderborght, Patricia R.
Katoch, Kiran
Mira, Marcelo T.
Thai, Vu Hong
Huong, Ngyuen Thu
Ba, Nguyen Ngoc
Moraes, Milton
Mehra, Narinder
Schurr, Erwin
Abel, Laurent
[J]. NATURE GENETICS, 2007, 39 (04) : 517 - 522
[4] [Anonymous], 1982, World Health Organ Tech Rep Ser, V675, P1
[5] Mycobacteria in Crohn's disease: A persistent hypothesis
Behr, Marcel A.
Schurr, Erwin
[J]. INFLAMMATORY BOWEL DISEASES, 2006, 12 (10) : 1000 - 1004
[6] Leprosy
Britton, WJ
Lockwood, DNJ
[J]. LANCET, 2004, 363 (9416) : 1209 - 1219
[7] Genetic dissection of immunity to mycobacteria: The human model
Casanova, JL
Abel, L
[J]. ANNUAL REVIEW OF IMMUNOLOGY, 2002, 20 : 581 - 620
[8] CHAKRAVARTTI MR, 1973, TOPICS HUMAN GENETIC, V1
[9] The genetics and immunopathogenesis of inflammatory bowel disease
Cho, Judy H.
[J]. NATURE REVIEWS IMMUNOLOGY, 2008, 8 (06) : 458 - 466
[10] The role of TNF superfamily members in T-cell function and diseases
Croft, Michael
[J]. NATURE REVIEWS IMMUNOLOGY, 2009, 9 (04) : 271 - 285

← 1 2 3 4 →