A susceptibility gene for type 2 diabetes confers substantial risk for diabetes complicating cystic fibrosis.
A susceptibility gene for type 2 diabetes confers substantial risk for diabetes complicating cystic fibrosis.
复制标题
DOI：
10.1007/s00125-009-1436-2
复制
发表时间：
2009-09
期刊：
影响因子：
8.2
通讯作者：
Cutting, G. R.
中科院分区：
文献类型：
--
作者：
Blackman, S. M.;Hsu, S.;Ritter, S. E.;Naughton, K. M.;Wright, F. A.;Drumm, M. L.;Knowles, M. R.;Cutting, G. R.
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. 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. 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). A genetic variant conferring risk for type 2 diabetes in the general population is a modifier of risk for diabetes in CF.
登录
查看更多内容
影响因子：
24.5
作者：
Ahmed, N;Corey, M;Durie, P
通讯作者：
Durie, P
影响因子：
2.1
作者：
Blangero, J;Williams, JT;Almasy, L
通讯作者：
Almasy, L
影响因子：
16.2
作者：
Cowie, Catherine C.;Engelgau, Michael M.;Gregg, Edward W.
通讯作者：
Gregg, Edward W.
影响因子：
5.1
作者：
Bismuth, Elise;Laborde, Kathleen;Robert, Jean-Jacques
通讯作者：
Robert, Jean-Jacques
影响因子：
158.5
作者：
Florez, Jose C.;Jablonski, Kathleen A.;Altshuler, David
通讯作者：
Altshuler, David