Human Leukocyte Antigen Class I Region Single-Nucleotide Polymorphisms are Associated with Leprosy Susceptibility in Vietnam and India

被引：42

作者：

Alter, Andrea ^{[1
,9
]}

Nguyen Thu Huong ^{[2
]}

Singh, Meenakshi ^{[3
]}

Orlova, Marianna ^{[1
,9
]}

Nguyen Van Thuc ^{[2
]}

Katoch, Kiran ^{[4
]}

Gao, Xiaojiang ^{[5
]}

Vu Hong Thai ^{[2
]}

Nguyen Ngoc Ba ^{[2
]}

Carrington, Mary ^{[5
,6
]}

Abel, Laurent ^{[7
,8
,10
]}

Mehra, Narinder ^{[3
]}

Alcais, Alexandre ^{[7
,10
]}

Schurr, Erwin ^{[1
,9
]}

机构：

[1] McGill Univ, McGill Ctr Study Host Resistance, Dept Med, Res Inst,Hlth Ctr, Montreal, PQ, Canada

[2] Hosp Dermatovenereol, Ho Chi Minh City, Vietnam

[3] All India Inst Med Sci, Dept Transplant Immunol & Immunogenet, New Delhi, India

[4] Cent JALMA Inst Leprosy & Other Infect Dis, Agra, Uttar Pradesh, India

[5] NCI Frederick, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD USA

[6] MGH MIT & Harvard Univ, Ragon Inst, Boston, MA USA

[7] Univ Paris 05, Fac Med Necker, Paris, France

[8] Rockefeller Univ, Rockefeller Branch, Lab Human Genet Infect Dis, New York, NY 10021 USA

[9] McGill Univ, McGill Ctr Study Host Resistance, Dept Human Genet, Res Inst,Hlth Ctr, Montreal, PQ, Canada

[10] INSERM, U550, Lab Genet Malad Infect, F-75654 Paris 13, France

来源：

JOURNAL OF INFECTIOUS DISEASES | 2011年 / 203卷 / 09期

基金：

加拿大健康研究院;

关键词：

HLA-C; QUANTITATIVE TRAITS; TUBERCULOID LEPROSY; GENETIC DISSECTION; DISEASE; POPULATION; EXPRESSION; RESISTANCE; SEQUENCE; IMMUNITY;

D O I：

10.1093/infdis/jir024

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Experimental evidence suggested the existence of unidentified leprosy susceptibility loci in the human leukocyte antigen (HLA) complex. To identify such genetic risk factors, a high-density association scan of a 1.9-mega-base (Mb) region in the HLA complex was performed. Among 682 single-nucleotide polymorphisms (SNPs), 59 were associated with leprosy (P <.01) in 198 Vietnamese single-case leprosy families. Genotyping of these SNPs in an independent sample of 292 Vietnamese single-case leprosy families replicated the association of 12 SNPs (P <.01). Multivariate analysis of these 12 SNPs showed that the association information could be captured by 2 intergenic HLA class I region SNPs (P = 9.4 x 10(-9))-rs2394885 and rs2922997 (marginal multivariate P = 2.1 x 10(-7) and P = .0016, respectively). SNP rs2394885 tagged the HLA-C*15:05 allele in the Vietnamese population. The identical associations were validated in a third sample of 364 patients with leprosy and 371 control subjects from North India. These results implicated class I alleles in leprosy pathogenesis.

引用

页码：1274 / 1281

页数：8

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