Contribution of alpha- and beta-defensins to lung function decline and infection in smokers: an association study.

Abstract

BACKGROUND:

Alpha-defensins, which are major constituents of neutrophil azurophilic granules, and beta-defensins, which are expressed in airway epithelial cells, could contribute to the pathogenesis of chronic obstructive pulmonary disease by amplifying cigarette smoke-induced and infection-induced inflammatory reactions leading to lung injury. In Japanese and Chinese populations, two different beta-defensin-1 polymorphisms have been associated with chronic obstructive pulmonary disease phenotypes. We conducted population-based association studies to test whether alpha-defensin and beta-defensin polymorphisms influenced smokers' susceptibility to lung function decline and susceptibility to lower respiratory infection in two groups of white participants in the Lung Health Study (275 = fast decline in lung function and 304 = no decline in lung function).

METHODS:

Subjects were genotyped for the alpha-defensin-1/alpha-defensin-3 copy number polymorphism and four beta-defensin-1 polymorphisms (G-20A, C-44G, G-52A and Val38Ile).

RESULTS:

There were no associations between individual polymorphisms or imputed haplotypes and rate of decline in lung function or susceptibility to infection.

CONCLUSION:

These findings suggest that, in a white population, the defensin polymorphisms tested may not be of importance in determining who develops abnormally rapid lung function decline or is susceptible to developing lower respiratory infections.

• Authors: Alison M Wallace, Jian-Qing He, Kelly M Burkett, Jian Ruan, John E Connett, Nicholas R Anthonisen, Peter D Paré, Andrew J Sandford
• Journal: Respiratory research (Respir Res) Vol. 7 Pg. 76 (May 15 2006) ISSN: 1465-993X [Electronic] England
• PMID: 16700921 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• alpha-Defensins
• beta-Defensins
• DNA

Topics

• Adult
• DNA (genetics)
• Female
• Gene Expression Regulation (physiology)
• Genetic Predisposition to Disease (genetics)
• Genotype
• Humans
• Linkage Disequilibrium (genetics)
• Lung (chemistry, physiopathology)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide (genetics)
• Pulmonary Disease, Chronic Obstructive (etiology, genetics, physiopathology)
• Respiratory Function Tests
• Respiratory Tract Infections (etiology, genetics)
• Smoking (adverse effects)
• alpha-Defensins (genetics, physiology)
• beta-Defensins (genetics, physiology)