Association of cystic fibrosis with abnormalities in fatty acid metabolism
Department of Pediatrics
Arachidonic Acid; Asthma; Biopsy; Case-Control Studies; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Docosahexaenoic Acids; Fatty Acids; Heterozygote; Humans; Inflammatory Bowel Diseases; Mutation; Nose; Rectum; Reference Values; Respiratory Tract Infections
Allergy and Immunology | Pediatrics | Respiratory Tract Diseases
BACKGROUND: Patients with cystic fibrosis have altered levels of plasma fatty acids. We previously demonstrated that arachidonic acid levels are increased and docosahexaenoic acid levels are decreased in affected tissues from cystic fibrosis-knockout mice. In this study we determined whether humans with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have a similar fatty acid defect in tissues expressing CFTR.
METHODS: Fatty acids from nasal- and rectal-biopsy specimens, nasal epithelial scrapings, and plasma were analyzed from 38 subjects with cystic fibrosis and compared with results in 13 obligate heterozygotes, 24 healthy controls, 11 subjects with inflammatory bowel disease, 9 subjects with upper respiratory tract infection, and 16 subjects with asthma.
RESULTS: The ratio of arachidonic to docosahexaenoic acid was increased in mucosal and submucosal nasal-biopsy specimens (P<0.001) and rectal-biopsy specimens (P=0.009) from subjects with cystic fibrosis and pancreatic sufficiency and subjects with cystic fibrosis and pancreatic insufficiency, as compared with values in healthy control subjects. In nasal tissue, this change reflected an increase in arachidonic acid levels and a decrease in docosahexaenoic acid levels. In cells from nasal mucosa, the ratio of arachidonic to docosahexaenoic acid was increased in subjects with cystic fibrosis (P<0.001), as compared with healthy controls, with values in obligate heterozygotes intermediate between these two groups (P<0.001). The ratio was not increased in subjects with inflammatory bowel disease. Subjects with asthma and those with upper respiratory tract infection had values intermediate between those in subjects with cystic fibrosis and those in healthy control subjects.
CONCLUSIONS: These data indicate that alterations in fatty acids similar to those in cystic fibrosis-knockout mice are present in CFTR-expressing tissue from subjects with cystic fibrosis.
DOI of Published Version
N Engl J Med. 2004 Feb 5;350(6):560-9. Link to article on publisher's site
The New England journal of medicine 15131835 15128902
Freedman SD, Blanco PG, Zaman MM, Shea JC, Ollero M, Hopper IK, Weed DA, Gelrud A, Regan MM, Laposata M, Alvarez JG, O'Sullivan BP. (2004). Association of cystic fibrosis with abnormalities in fatty acid metabolism. Pulmonary and Allergy. https://doi.org/10.1056/NEJMoa021218. Retrieved from https://escholarship.umassmed.edu/peds_pulmonary/7