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Depts of 1 Cellular and Molecular Physiology, 5 Pediatrics, and 2 Health Evaluation Sciences, The Pennsylvania State University College of Medicine,Hershey, PA, USA. 3 National institute of Respiratory Diseases. 4 Dept of Science National Autonymous University of Mexico, Mexico
CORRESPONDENCE: J. Floros, Dept of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, 500 University Drive, H166 Hershey, PA 17033, USA. Fax: 1 7175317667
Keywords: chronic obstructive pulmonary disease, gene interaction, surfactant protein, surfactant proteins A, B and D
Received: May 12, 2000
Accepted May 9, 2001
This work was supported by NIH R37 HL34788 and the General Clinical Research Center at the Pennsylvania State University College of Medicine.
Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation. It is most likely the result of complex interactions of environmental and genetic factors. Because pulmonary surfactant components play important roles in normal lung function, innate host defence, and inflammation in the lung, this study investigated the hypothesis that the surfactant protein genes are involved in certain cases of COPD.
Genotype analysis of surfactant protein (SP)-A, SP-B, SP-B-linked microsatellite, and SP-D marker alleles was performed in patients with COPD (n=97) and smoker (n=82) or nonsmoker (n=99) controls. Univariate and multiple logistic regression analyses were performed.
The regression analysis results between COPD and smokers revealed several COPD susceptibility alleles (AA62_A, B1580_C, D2S388_5), based on an odds ratio (OR >2.5). The predictive ability of this model for developing COPD is good (c=0.926). Allele-allele (B1580_C and D2S388_5) and allele-environment (i.e. smoking) interactions were detected. When smoker controls were compared to nonsmoker controls, marker D2S388_5 appeared to be smoking-independent (p=0.874), whereas marker alleles AA62_A (p=0.045) and B1580_5 (p=0.007) were smoking-dependent. Males were at higher risk (OR=6.05, p=0.001), and smoking (>50 packs·yr–1) increased risk (OR=5.38, p=0.007). Males and alleles of loci flanking SP-B were associated with more severe cases (forced expiratory volume in one second/forced vital capacity
The present results indicate that the surfactant protein alleles may be useful in chronic obstructive pulmonary disease by either predicting the disease in a subgroup and/or by identifying disease subgroups that may be used for therapeutic intervention. These observations should now be confirmed in a larger study, designed according to strict epidemiological criteria.
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