Update on gene modifiers in cystic fibrosis.
OBJECTIVE
Cystic fibrosis (CF) is a common, life-limiting monogenic disease, which typically manifests as progressive bronchiectasis, exocrine pancreatic dysfunction, and recurrent sinopulmonary infections. Although the gene responsible for CF (CFTR) was described in 1989, it has become increasingly evident that modifier genes and environmental factors play substantial roles in determining the severity of disease, particularly lung disease. Identifying these factors is crucial in devising therapies and other interventions to decrease the morbidity and mortality associated with this disorder.


RESULTS
Although many genes have been proposed as potential modifiers of CF, only a handful have withstood the test of replication. Several of the replicated findings reveal that genes affecting inflammation and infection response play a key role in modifying CF lung disease severity. Interactions between CFTR genotype, modifier genes, and environmental factors have been documented to influence lung function measures and infection status in CF patients.


CONCLUSIONS
Several genes have been demonstrated to affect disease severity in CF. Furthermore, it is likely that gene-gene and gene-environment interactions can explain a substantial portion of the variation of lung disease. Ongoing genome-wide studies are likely to identify novel genetic modifiers. Continued exploration of the role of genetic and nongenetic modifiers of CF is likely to yield new options for combating this debilitating disease.
Collaco
Joseph M
JM
Eudowood Division of Pediatric Respiratory Sciences, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Cutting
Garry R
GR
D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D006801:Humans; D037601:Mannose-Binding Lectin / Q000235:genetics; D012720:Severity of Illness Index; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
C505032:CFTR protein, human; C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D019005:Cystic Fibrosis Transmembrane Conductance Regulator