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PMID: 17570749 Published · ppublish English Clinical Trial Journal Article Research Support, Non-U.S. Gov't

Genetic prediction of future type 2 diabetes.

PLoS medicine ·Vol. 2 ·No. 12 ·2005-11-01 ·Pages e345

Lyssenko V, Almgren P, Anevski D, Orho-Melander M, Sjögren M, Saloranta C, Tuomi T, Groop L, Botnia Study Group

Abstract

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. 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 > or = 5.6 mmol/l and body mass index > or = 30 kg/m(2), 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/m(2). 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.

MeSH Terms
Adolescent Adult Aged Blood Glucose Body Mass Index Diabetes Mellitus, Type 2/genetics Female Finland Genetic Predisposition to Disease Genotype Humans Male Middle Aged Polymorphism, Single Nucleotide Predictive Value of Tests Prospective Studies Risk Factors
Chemicals
Blood Glucose
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Lyssenko Valeriya
Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, University Hospital Malmö, Malmö, Sweden. [email protected]
Almgren Peter
Anevski Dragi
Orho-Melander Marju
Sjögren Marketa
Saloranta Carola
Tuomi Tiinamaija
Groop Leif
Botnia Study Group
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41 references, click to expand
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Article Info
Journal
PLoS medicine
Abbr.
PLoS Med
ISSN
1549-1676
DOI
10.1371/journal.pmed.0020345
Email
[email protected]
Published
2005-11-01
Pages
e345
Language
English
Region
United States
NLM ID
101231360
PMCID
PMC1274281
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pmed.0020345 PMC Full Text View journal details
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