Genetic prediction of future type 2 diabetes
Journal article, 2005

Background: Type 2 diabetes (T2D) is a multifactorial disease in which environmental triggers interact with genetic variants in the predisposition to the disease. A number of common variants have been associated with T2D but our knowledge of their ability to predict T2D prospectively is limited. Methods and Findings: By using a Cox proportional hazard model, common variants in the PPARG (P12A), CAPN10 (SNP43 and 44), KCNJ11 (E23K), UCP2 (-866G>A), and IRS1 (G972R) genes were studied for their ability to predict T2D in 2,293 individuals participating in the Botnia study in Finland. After a median follow-up of 6 y, 132 (6%) persons developed T2D. The hazard ratio for risk of developing T2D was 1.7 (95% confidence interval [CI] 1.1-2.7) for the PPARG PP genotype, 1.5 (95% CI 1.0-2.2) for the CAPN10 SNP44 TT genotype, and 2.6 (95% CI 1.5-4.5) for the combination of PPARG and CAPN10 risk genotypes. In individuals with fasting plasma glucose ≥ 5.6 mmol/l and body mass index ≥ 30 kg/m2, the hazard ratio increased to 21.2 (95% CI 8.7-51.4) for the combination of the PPARG PP and CAPN10 SNP43/44 GG/TT genotypes as compared to those with the low-risk genotypes with normal fasting plasma glucose and body mass index < 30 kg/m2. Conclusion: We demonstrate in a large prospective study that variants in the PPARG and CAPN10 genes predict future T2D. Genetic testing might become a future approach to identify individuals at risk of developing T2D.

Author

V. Lyssenko

Lund University

P. Almgren

Lund University

Dragi Anevski

University of Gothenburg

Chalmers, Mathematical Sciences, Mathematical Statistics

M. Orho-Melander

Lund University

M. Sjögren

Lund University

C. Saloranta

Helsinki University Central Hospital

Folkhalsan

T. Tuomi

Helsinki University Central Hospital

Folkhalsan

L. Groop

Lund University

PLoS Medicine

1549-1277 (ISSN) 1549-1676 (eISSN)

Vol. 2 12 1299-1308

Subject Categories

Probability Theory and Statistics

DOI

10.1371/journal.pmed.0020345

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3/2/2018 9