Association of polymorphisms of the transporter associated with antigen processing (TAP2) gene with pulmonary tuberculosis in an elderly Japanese population.
The transporter associated with antigen processing 2 (TAP2) gene is involved in the immunological response to tuberculosis (TB) infection. Variations in the TAP2 gene have been associated with TB infection in small population studies in India, Columbia, and Korea. We investigated the association of TAP2 polymorphisms with TB susceptibility in an elderly Japanese population. We analyzed samples from consecutive autopsy cases (n = 1850) registered in the Japanese Geriatric SNP Research database. TB was diagnosed pathologically by TB granuloma on autopsy samples. There were 289 cases and 1529 controls. Twenty-four single nucleotide variations (SNVs), including four missense variations in the TAP2 region, were genotyped using the Illumina Infinium Human Exome BeadChip array. Of the 24 SNVs in the TAP2 gene, rs4148871, rs4148876 (R651C), and rs2857103 showed statistically significant associations with TB susceptibility, and rs4148871 and rs2857103 also showed significant genotypic associations in a dominant allele model adjusted for age, sex, and smoking. Haplotype analysis showed that TAP2 allele *0103 conferred an increased TB risk (OR = 1.48, p = 0.0008), while the TAP2 *0201 allele was protective against TB (OR = 0.73, p = 0.0007). Our results suggest that TAP2 polymorphisms influence TB susceptibility in a Japanese population.
Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Kaung Si
KS
Thu
Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Noriko
N
Sato
Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Shinobu
S
Ikeda
Department of Medical Informatics, Center of Information, Jichii Medical University, Tochigi, Japan.
Makiko
M
Naka-Mieno
Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan.|Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
Tomio
T
Arai
Center for Promotion of Clinical Investigation, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan.
Seijiro
S
Mori
Department of Moleculo-genetic Sciences, Division of Biomedical Laboratory Sciences, Molecular Pathophysiology, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Motoji
M
Sawabe
Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Masaaki
M
Muramatsu
Department of Genomics for Longevity and Health, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
Masashi
M
Tanaka
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3 / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D020641:Polymorphism, Single Nucleotide; D014397:Tuberculosis, Pulmonary / Q000235:genetics*
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; C071692:TAP2 protein, human
Transporter associated with antigen processing (TAP2); non-synonymous variants; single-nucleotide variants; susceptibility; tuberculosis