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* From the Departments of Cellular and Molecular Physiology (Drs. Zhenwu Lin, Guo, Wang, and DiAngelo) and Pediatrics (Dr. Floros), and Health Evaluation Sciences (Dr. Hung-Mo Lin), Pennsylvania State University College of Medicine, Hershey, PA; Instituto Nacional de Enfermedades Respiratorias (Drs. Sansores and Selmon, Ms. Montaño), and Facultad de Ciencias UNAM (Dr. Pardo), Mexico.
Correspondence to: Joanna Flores, PhD, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033
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Introduction |
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 TOP Introduction References |
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1-antitrypsin is one of the documented risk factors,
this accounts for < 1% of the COPD cases.1
4
Other
genetic polymorphisms have been associated with increased
susceptibility to developing COPD.5
6
In addition, the
expression of the disease itself is complex, ie, some COPD
patients may develop predominately airway disease and others
parenchymal disease. Pulmonary surfactant, a lipoprotein complex, is essential for normal lung function.7 In addition, pulmonary surfactant or its components are shown to play important roles in the innate host defense of the lung and the regulation of inflammatory processes.8 Because there is a chronic inflammation in COPD, and because deranged surfactant composition has the potential to contribute to both surfactant dysfunction and to altered defenses and altered regulation of inflammatory processes in the lung, we reasoned that the surfactant system is a good candidate to be considered in studies where etiologic factors of COPD are being investigated.
Toward this goal, we wished first to gain insight as to whether pulmonary surfactant is important in the pathogenesis of COPD, by carrying out association studies of polymorphisms in the surfactant protein genes and individuals with COPD (FEV1 < 70% predicted, and FEV1/FVC < 70%), healthy smokers FEV1 > 70% predicted, and FEV1/FVC > 70%), and healthy nonsmokers.
Specifically, we genotyped these groups of individuals for polymorphic loci within the SP-A,9 11 SP-B,10 and SP-D11 genes, and microsatellite markers flanking the SP-B gene.12 We then analyzed the data by performing univariate and multivariate logistic regression analysis between COPD vs healthy controls, and COPD vs smokers. The univariate analysis revealed, for the COPD vs control comparison, significant differences for alleles of SP-A, SP-D, and alleles of some of the microsatellite markers. For the COPD vs smokers, significant differences (p < 0.05) were observed for alleles of SP-A, SP-B, and alleles of some of the microsatellites. However, among the differences observed in the two sets of comparisons, only one allele of one of the microsatellite markers was found to be in common.
Next, we performed multivariate logistic regression analysis using a
backward selection with = 0.05. In the first multivariate
analysis, we considered all the marker alleles under study; in the
second multivariate analysis, we considered only alleles, the frequency
of which was shown to differ significantly (p < 0.05) in the
univariate analysis. Although a number of alleles were found to be in
common in both types of multivariate analyses of each set of
comparisons (ie, COPD vs healthy control, and COPD vs
healthy smoker), the only marker that was in common in both sets of
comparisons was the microsatellite allele shown to be in common in the
univariate analysis. Furthermore, the frequency of this microsatellite
allele was not significantly different when the control and smoker
groups were compared, suggesting specificity to COPD. Based on the odds
ratio, this allele (or a linked locus) may be viewed as a
susceptibility factor to COPD. We further speculate, based on the
overall univariate and multivariate findings, that some of the alleles
(p < 0.05) play a role in the pathogenesis of COPD by increasing
susceptibility to COPD or protecting from developing COPD when these
are found in certain genetic background or under the influence of a
certain environment.
In summary, the surfactant protein gene loci and flanking loci may serve as useful markers in the study of etiologic factors for COPD.
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Footnotes |
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References |
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TOPIntroductionReferences |
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1-antitrypsin deficiency of adults with pulmonary symptoms. Am Rev Respir Dis 138,327-336[ISI][Medline]
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