RGD Reference Report - A susceptibility gene for type 2 diabetes confers substantial risk for diabetes complicating cystic fibrosis. - Rat Genome Database

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A susceptibility gene for type 2 diabetes confers substantial risk for diabetes complicating cystic fibrosis.

Authors: Blackman, SM  Hsu, S  Ritter, SE  Naughton, KM  Wright, FA  Drumm, ML  Knowles, MR  Cutting, GR 
Citation: Blackman SM, etal., Diabetologia. 2009 Sep;52(9):1858-65. Epub 2009 Jul 8.
RGD ID: 2312417
Pubmed: PMID:19585101   (View Abstract at PubMed)
PMCID: PMC2877501   (View Article at PubMed Central)
DOI: DOI:10.1007/s00125-009-1436-2   (Journal Full-text)

AIMS/HYPOTHESIS: Insulin-requiring diabetes affects 25-50% of young adults with cystic fibrosis (CF). Although the cause of diabetes in CF is unknown, recent heritability studies in CF twins and siblings indicate that genetic modifiers play a substantial role. We sought to assess whether genes conferring risk for diabetes in the general population may play a risk modifying role in CF. METHODS: We tested whether a family history of type 2 diabetes affected diabetes risk in CF patients in 539 families in the CF Twin and Sibling family-based study. A type 2 diabetes susceptibility gene (transcription factor 7-like 2, or TCF7L2) was evaluated for association with diabetes in CF using 998 patients from the family-based study and 802 unrelated CF patients in an independent case-control study. RESULTS: Family history of type 2 diabetes increased the risk of diabetes in CF (OR 3.1; p = 0.0009). A variant in TCF7L2 associated with type 2 diabetes (the T allele at rs7903146) was associated with diabetes in CF in the family study (p = 0.004) and in the case-control study (p = 0.02; combined p = 0.0002). In the family-based study, variation in TCF7L2 increased the risk of diabetes about three-fold (HR 1.75 per allele, 95% CI 1.3-2.4; p = 0.0006), and decreased the mean age at diabetes diagnosis by 7 years. In CF patients not treated with systemic glucocorticoids, the effect of TCF7L2 was even greater (HR 2.9 per allele, 95% CI 1.7-4.9, p = 0.00011). CONCLUSIONS/INTERPRETATION: A genetic variant conferring risk for type 2 diabetes in the general population is a modifier of risk for diabetes in CF.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
diabetes mellitus  IAGP 2312417associated with Cystic Fibrosis and DNA:SNP (human)RGD 
diabetes mellitus  ISOTCF7L2 (Homo sapiens)2312417; 2312417associated with Cystic Fibrosis and DNA:SNP (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tcf7l2  (transcription factor 7 like 2)

Genes (Mus musculus)
Tcf7l2  (transcription factor 7 like 2, T cell specific, HMG box)

Genes (Homo sapiens)
TCF7L2  (transcription factor 7 like 2)


Additional Information