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JCI table of contents: Feb. 21, 2008
Date:2/21/2008

EDITOR'S PICK: Deficiency in the protein MBL2 is linked to increased cystic fibrosis severity

Cystic fibrosis (CF), a hereditary disorder causing thick mucous production and frequent lung infections, is associated with a high mortality rate primarily due to lung failure. Although it is known that mutations in the CFTR gene cause the disease, variations in other genes between individuals with CF modify the severity of the disease. For example, the gene responsible for making the MBL2 protein has been suggested to modify lung function in individuals with CF; however, its precise roles in the disease have not been well understood. In a new study, Julian Zielenski and his colleagues at the Hospital for Sick Children, Toronto, found that genetic variations that modify MBL2 expression were associated with more severe clinical symptoms of CF.

The researchers compared levels of MBL2 in the blood of more than 1,000 CF patients and found that patients deficient in MBL2 were often younger when first infected with the bacteria Pseudomonas aeruginosa, and that their lung function declined more rapidly than patients with normal or high levels of the protein. These associations between MBL2 and CF severity were even more pronounced in patients that overproduced the protein TGF-beta-1. The authors argue that these findings might provide a basis for new approaches for treating those individuals with CF who are at risk of such increased disease severity. In an accompanying commentary, Frank Accurso and Marci Sontag at the University of Colorado Denver further suggest that it might be useful to screen for gene variants that cause the production of high levels of MBL2 and TGF-beta-1, as well as other genes that modify the course of CF, in newborn CF screening.

TITLE: Complex two-gene modulation of lung disease severity in children with cystic fibrosis

AUTHOR CONTACT:
Julian Zielenski
Hospital for Sick Children, Toronto, Ontario
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Contact: Karen Honey
press_releases@the-jci.org
215-573-1850
Journal of Clinical Investigation
Source:Eurekalert

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