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Update on gene modifiers in cystic fibrosis Collaco JM; Cutting GRCurr Opin Pulm Med 2008[Nov]; 14 (6): 559-66PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.|Cystic Fibrosis Transmembrane Conductance Regulator/*genetics[MESH]|Cystic Fibrosis/*genetics[MESH]|Humans[MESH]|Mannose-Binding Lectin/genetics[MESH]|Severity of Illness Index[MESH]|Transforming Growth Factor beta1/genetics[MESH]|Tumor Necrosis Factor-alpha/genetics[MESH] |
