Modifier genes and variation in cystic fibrosis

Abstract

The availability of molecular tools to carry out genotyping has led to a flurry of association studies between specific genes and clinical indices of disease or disease susceptibility. Human studies, for the most part, have a limited number of subjects available, precluding whole genome types of approaches. 'Candidate gene' strategies have consequently become widespread, probably in part due to the inherent similarity to clinical association studies. Such studies in cystic fibrosis have found tantalizing results in genes involved in infection and inflammation, but many other relevant pathways remain untapped. Genome scanning approaches may eventually uncover genes not currently recognized as important to cystic fibrosis. In the meantime, while thousands of polymorphisms are cataloged and other genomic resources become more available, the number of association studies with candidate genes will no doubt increase. To make sense of these studies, the choice of gene and phenotype must be carefully considered.

Figure 1

Potential sites for the effects of CF airway modifiers. Genes that affect the expression of CFTR, processing of the CFTR protein, or activity of ion channels in the epithelium, as well as control of mucus production and mucociliary clearance (left), could all have an impact on the sequence of events in the CF lung. Genes that influence the consequences of the defects at the epithelium, such as infection, chemotactic signals of inflammation, and tissue remodeling, would also be likely to modify clinical manifestations of the disease.