From Johns Hopkins: Genetic modifiers of cystic fibrosis-related diabetes

http://www.ncbi.nlm.nih.gov/pubmed/23670970

Diabetes. 2013 May 13. [Epub ahead of print]

Genetic modifiers of cystic fibrosis-related diabetes.

Blackman SM, Commander CW, Watson C, Arcara KM, Strug LJ, Stonebraker JR, Wright FA, Rommens JM, Sun L, Pace RG, Norris SA, Durie PR, Drumm ML,Knowles MR, Cutting GR.

Source

Division of Pediatric Endocrinology, Johns Hopkins University School of Medicine, Baltimore, MD.

Abstract

Diabetes is a common age-dependent complication of cystic fibrosis (CF) that is strongly influenced by modifier genes. We conducted a genome-wide association study in 3059 individuals with CF (644 with CFRD) and identified single nucleotide polymorphisms (SNPs) within and 5' to the SLC26A9 gene which associated with CFRD (hazard ratio=1.38, P=3.6×10^-8). Replication was demonstrated in 694 individuals (124 with CFRD) (hazard ratio=1.47, P=0.007) with combined analysis significant at P=9.8×10^-10. SLC26A9 is an epithelial chloride/bicarbonate channel that can interact with CFTR, the protein mutated in CF. We also hypothesized that common SNPs associated with type 2 diabetes (T2D SNPs) might also affect risk for CF-related diabetes (CFRD). A previous association of CFRD with SNPs in TCF7L2 was replicated in this study (P=0.004; combined analysis P=3.8×10^-6), and T2D SNPs at/near CDKAL1, CDKN2A/B, and IGF2BP2 associated with CFRD (P<0.004). These 5 loci accounted for 8.3% of the phenotypic variance in CFRD onset and had a combined population attributable risk of 68%. Diabetes is a highly prevalent complication of CF whose susceptibility is determined in part by variants at SLC26A9 (which mediates processes proximate to the CF disease-causing gene), and at 4 susceptibility loci for type 2 diabetes in the general population.