Association of cystic fibrosis with abnormalities in fatty acid metabolism.
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.
Freedman
Steven D
SD
Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA. sfreedma@caregroup.harvard.edu
Blanco
Paola G
PG
Zaman
Munir M
MM
Shea
Julie C
JC
Ollero
Mario
M
Hopper
Isabel K
IK
Weed
Deborah A
DA
Gelrud
Andres
A
Regan
Meredith M
MM
Laposata
Michael
M
Alvarez
Juan G
JG
O'Sullivan
Brian P
BP
D016718:Arachidonic Acid / Q000378:metabolism*; D001249:Asthma / Q000378:metabolism; D001706:Biopsy; D016022:Case-Control Studies; D003550:Cystic Fibrosis / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism; D009154:Mutation; D009297:Nasal Mucosa / Q000378:metabolism; D012007:Rectum / Q000378:metabolism; D012016:Reference Values; D012141:Respiratory Tract Infections / Q000378:metabolism
C505032:CFTR protein, human; D005227:Fatty Acids; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid