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Polymorphisms in the CD14 Gene Associated with Pulmonary Function in Farmers

Arizona Respiratory Center and Departments of Internal Medicine and Pediatrics, College of Medicine, University of Arizona, Tucson, Arizona; Department of Exercise Science and Athletic Training, Creighton University; Department of Internal Medicine, Pulmonary and Critical Care Medicine Section, University of Nebraska Medical Center, Omaha, Nebraska; and Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, Iowa

Correspondence and requests for reprints should be addressed to Susanna Von Essen, M.D., M.P.H., Department of Internal Medicine, Pulmonary and Critical Care Medicine Section, University of Nebraska, Omaha, NE 68198-5300. E-mail: svonesse{at}unmc.edu

Rationale and Objectives: Farmers experience airway obstruction, which may be attributable in part to endotoxin inhalation. CD14 is a receptor for endotoxin. Materials and Methods: Based on our findings of increased circulating CD14 associated with the CD14/–159 T allele, we hypothesized that carriers of this allele would have decreased lung function among endotoxin-exposed individuals. CD14/–159TT farmers (n = 19) had significantly lower lung function as measured by FEV₁ (p = 0.028) and mean forced expiratory flow during the middle half of the FVC (FEF_25–75) (p = 0.05) compared with farmers with the C allele (n = 78). Also, farmers with the CD14/–1619GG genotype (n =11) were associated with lower lung function (FEV₁, p = 0.008; FEF_25–75, p = 0.009) compared with farmers with the A allele (n = 86). Results: No association between CD14/–550 and lung function was observed (FEV₁, p = 0.32; FEF_25–75, p = 0.11). Increased prevalence of wheezing was reported in farmers homozygous for CD14/–159T (p = 0.013) or CD14/–1619G (p = 0.019) compared with farmers with the CC or AA genotype, respectively. No association was found between TLR4/Asp299Gly and lung function or wheeze. Conclusion: We conclude that the CD14/–159 or CD14/–1619 loci may play a role in modulating lung function and wheeze among agricultural workers.

Key Words: endotoxin • farming • lipopolysaccharide • occupational exposure • wheeze

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