An exome wide association study of pulmonary tuberculosis patients and their asymptomatic household contacts |
| |
| Institution: | 1. Kunming National High-level Biosafety Research Center, Chinese Academy of Medical Science, Institute of Medical Biology, China;2. Kunming City Center for Disease Control and Prevention, China;1. Grupo de Medicina Xenómica, Centro de Investigación en Medicina Molecular e Enfermidades Crónicas da Universidade de Santiago de Compostela (CIMUS), Avda. Barcelona s/n, 15782 Santiago, Galicia, Spain;2. Xenómica Comparada de Parasitos Humanos, Instituto de Investigacións Sanitarias de Santiago (IDIS), Travesia da Choupana s/n, 15706 Santiago, Galicia, Spain;3. Servizo de Microbioloxía e Parasitoloxía, Complexo Hospitalario Universitario de Santiago, Travesia da Choupana s/n, 15706 Santiago, Galicia, Spain;1. Department of Molecular Medicine, Sapienza University of Rome, Italy;2. Department of Paediatrics, Sapienza University of Rome, Italy;1. Division of Clinical Research, The First Hospital of Jilin University, Changchun, Jilin 130021, China;2. Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100020, China;3. Division of Education, Beijing Jishuitan Hospital, Beijing 100020, China;4. Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin 130021, China;5. Maternal and Child Health Center of Chaoyang District, Beijing 100020, China;1. KU Leuven, Department of Microbiology and Immunology, Rega Institute, Laboratory of Evolutionary and Computational Virology, 3000, Leuven, Belgium;2. Baqiyatallah Research Center for Gastroenterology and Liver Disease, Baqiyatallah University of Medical Sciences, Tehran, Iran;3. Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, 4032 Debrecen, Hungary;4. Biosafety Development Group, Cellular Sciences Department, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA;5. KU Leuven, Department of Microbiology and Immunology, Rega Institute, Laboratory of Clinical and Epidemiological Virology, 3000, Leuven, Belgium;6. Blood Transfusion Research Centre, High Institute for Research and Education in Transfusion Medicine, Hemmat Exp. Way, 14665-1157, Tehran, Iran |
| |
| Abstract: | Tuberculosis is a leading cause of death in India. To identify genetic variants associated with susceptibility or resistance to Mycobacterium tuberculosis infection, we have performed an exome-wide association study with 0.2 million exonic variants among 119 pairs of tuberculosis patients and their clinically asymptomatic household contacts. The strongest association was identified for rs61104666A], a synonymous variant (p.E292E) of exon 5 of the gene SIGLEC15 (OR = 2.4, p = 1.49 × 10?5). We also found association of non-coding variants in the 3′UTR region of a gene encoding the class II human leukocyte antigens (HLAs), HLA-DRA. rs13209234A] (minor allele frequency (MAF) = 13.8%) (OR = 0.35, P = 2.5 × 10?4) and rs3177928A] (minor allele frequency (MAF) = 13.7%) (OR = 0.35, P = 3.3 × 10?4) were associated with protection from tuberculosis. These two SNPs, rs13209234 and rs3177928, are in complete linkage disequilibrium. These associations remained valid when additional data on freshly recruited individuals were jointly analyzed on 250 patient-control pairs. The identified gene, HLA-DRA, suggest involvement of immune regulation, indicating pathways associated with antigen presentation in tuberculosis infection. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
