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Contribution of TAP genes to genetic predisposition for diffuse panbronchiolitis
N Keicho1, K Tokunaga, K Nakata
1Department of Respiratory Medicine, University of Tokyo, Japan. KEICHO-3Im@h.u.tokyo.ac.jp
Tissue Antigens
|May 14, 1999
Summary
Genetic factors in the human leukocyte antigen (HLA) region influence diffuse panbronchiolitis susceptibility in Asians. Specific variations in the TAP2 gene are associated with this chronic obstructive pulmonary disease.
Area of Science:
- Pulmonary Medicine
- Immunogenetics
- Human Genetics
Background:
- Diffuse panbronchiolitis (DPB) is a chronic obstructive pulmonary disease prevalent in Asian populations.
- Genetic predisposition is suspected in DPB etiology, with prior studies linking human leukocyte antigen (HLA)-B54 to disease susceptibility.
- Impaired class I molecule expression has been observed in conditions resembling DPB, suggesting a role for the class I antigen presenting system.
Purpose of the Study:
- To investigate the association of genes within the HLA region, specifically TAP1, TAP2, and LMP2, with diffuse panbronchiolitis.
- To determine if genetic variations in the class I antigen presenting pathway contribute to DPB pathogenesis.
- To clarify the genetic underpinnings of DPB susceptibility in Asian populations.
Main Methods:
- Analysis of TAP1, TAP2, and LMP2 genes in 76 DPB patients and 120 healthy controls.
- Genotyping for specific alleles and substitutions within the selected HLA-region genes.
- Statistical analysis to assess the association between genetic variations and DPB, considering linkage disequilibrium with HLA-B alleles.
Main Results:
- A significant association was found between the TAP2 gene (Ala-665 and Gln-687 combination) and DPB (P=0.0028, Pc<0.05).
- This TAP2 variation showed disease association independent of HLA-B*5401, suggesting a direct role beyond linkage disequilibrium.
- A negative association was observed for the His-60 substitution in the LMP2 gene, potentially explained by linkage with HLA-B44.
Conclusions:
- Genetic factors within the human leukocyte antigen (HLA) region contribute to the susceptibility of diffuse panbronchiolitis.
- Variations in genes involved in the class I antigen presenting system, such as TAP2, may play a role in DPB pathogenesis.
- These findings support a multifactorial etiology for DPB, involving both class I genes and related antigen-presenting molecules.
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