1. ¹Medical Genetic Section, National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand
2. ²TB/HIV Research Project, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Chiang Rai, Thailand
3. ³Center for Collaborative Research and Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan
4. ⁴Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan
5. ⁵Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
6. ⁶Department of Respiratory Diseases, Research Institute, International Medical Center of Japan, Shinjuku-ku, Tokyo, Japan
7. ⁷Chiang Rai Provincial Health Office, Ministry of Public Health, Chiang Rai, Thailand
8. ⁸Chest Disease Institute, Department of Medical Services, Ministry of Public Health, Nonthaburi, Thailand
9. ⁹Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
10. ¹⁰Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, Thailand
11. ¹¹Chiang Rai Regional Hospital, Ministry of Public Health, Chiang Rai, Thailand
12. ¹²Chiang Rai Regional Medical Sciences Center, Department of Medical Sciences, Ministry of Public Health, Chiang Rai, Thailand
13. ¹³Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

Correspondence: Dr N Keicho, Department of Respiratory Diseases, Research Institute, International Medical Center of Japan, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan. E-mail: nkeicho-tky@umin.ac.jp

Received 30 June 2008; Revised 11 August 2008; Accepted 27 August 2008; Published online 9 October 2008.

Abstract

Tuberculosis, a potentially fatal infectious disease, affects millions of individuals annually worldwide. Human protective immunity that contains tuberculosis after infection has not been clearly defined. To gain insight into host genetic factors, nonparametric linkage analysis was performed using high-throughput microarray-based single nucleotide polymorphism (SNP) genotyping platform, a GeneChip array comprised 59 860 bi-allelic markers, in 93 Thai families with multiple siblings, 195 individuals affected with tuberculosis. Genotyping revealed a region on chromosome 5q showing suggestive evidence of linkage with tuberculosis (Z(lr) statistics=3.01, logarithm of odds (LOD) score=2.29, empirical P-value=0.0005), and two candidate regions on chromosomes 17p and 20p by an ordered subset analysis using minimum age at onset of tuberculosis as the covariate (maximum LOD score=2.57 and 3.33, permutation P-value=0.0187 and 0.0183, respectively). These results imply a new evidence of genetic risk factors for tuberculosis in the Asian population. The significance of these ordered subset results supports a clinicopathological concept that immunological impairment in the disease differs between young and old tuberculosis patients. The linkage information from a specific ethnicity may provide unique candidate regions for the identification of the susceptibility genes and further help elucidate the immunopathogenesis of tuberculosis.