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Diabetologia. 2009 Sep;52(9):1858-65. doi: 10.1007/s00125-009-1436-2. Epub 2009 Jul 8.

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

Author information

1
Division of Pediatric Endocrinology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Abstract

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.

PMID:
19585101
PMCID:
PMC2877501
DOI:
10.1007/s00125-009-1436-2
[Indexed for MEDLINE]
Free PMC Article

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