Role of genetic susceptibility to latent adenoviral infection and decreased lung function - 07/08/11

Doi : 10.1016/j.rmed.2009.05.008

Ikuma Kasuga, James C. Hogg, Peter D. Paré, Shizu Hayashi, Edward G. Sedgwick, Jian Ruan, Alison M. Wallace, Jian-Qing He, Xiaozhu Zhang, Andrew J. Sandford ^⁎
The James Hogg iCAPTURE Centre, University of British Columbia, St Paul’s Hospital, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada

Corresponding author. Tel.: +1 604 806 9008; fax: +1 604 806 8351.

Summary

Background

Latent adenoviral infection may amplify cigarette smoke-induced lung inflammation and therefore play an important role in the development of chronic obstructive pulmonary disease (COPD). Adenoviruses can evade the human immune response via their 19-kDa protein (19K) which delays the expression of class I human leukocyte antigen (HLA) proteins. The 19K protein shows higher affinity to HLA-B7 and A2 compared with HLA-A1 and A3. The receptor for adenovirus (CXADR) and integrin β₅ (ITGB5) are host factors which might affect adenovirus infection. Therefore, we investigated the contribution of HLA, CXADR, and ITGB5 genetic variants to the presence of the E1A gene and to level of lung function.

Methods

Study subjects were assayed for HLA-B7, A1, A2 and A3 by PCR-based assays using allele-specific primers. Polymorphisms of the CXADR and ITGB5 genes were genotyped by PCR-based restriction fragment length polymorphism assays. Detection of adenoviral E1A gene was performed by a real-time PCR TaqMan assay.

Results

E1A positive individuals had a lower FEV₁ compared with E1A negative individuals. However, there was no significant difference in E1A positivity rate between the high (HLA-B7 and A2) and low (HLA-A1 and A3) 19K affinity groups. There was also no significant difference in FEV₁ level between each affinity group. There was no significant difference in E1A positivity rate or lung function among the CXADR and ITGB5 genotypes.