Genetic prediction of future type 2 diabetes.
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.


RESULTS
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).


CONCLUSIONS
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.
Lyssenko
Valeriya
V
Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, University Hospital Malmö, Malmö, Sweden. Valeri.Lyssenko@med.lu.se
Almgren
Peter
P
Anevski
Dragi
D
Orho-Melander
Marju
M
Sjögren
Marketa
M
Saloranta
Carola
C
Tuomi
Tiinamaija
T
Groop
Leif
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005387:Finland; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors
D001786:Blood Glucose