Association of the FTO gene variant (rs9939609) with cardiovascular disease in men with abnormal glucose metabolism--the Finnish Diabetes Prevention Study.
OBJECTIVE
The common single nucleotide polymorphism (SNP) in the FTO (fat mass and obesity associated) gene has been consistently associated with an increased risk of obesity. We investigated whether the SNP rs9939609 (T/A) of the FTO is associated with risk factors of cardiovascular diseases (CVD), including serum levels of C - reactive protein (CRP), the chemokine RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted; CCL5), and serum and lipoprotein lipids in the Finnish Diabetes Prevention Study (DPS). Furthermore, we examined whether the rs9939609 increased the CVD risk in the DPS and if these results could be replicated in a larger cross-sectional population-based random sample of Finnish men (the METSIM).


RESULTS
In the DPS, altogether 490 (BMI≥25kg/m(2)) subjects with impaired glucose tolerance were genotyped for rs9939609. Cardiovascular morbidity and mortality data were collected during the median follow-up of 10.2 years. The replication study was a population-based cross-sectional study of 6214 men. In the DPS, the AA genotype of rs9939609 was associated, independently of BMI, with increased RANTES (p=0.002) and decreased HDL cholesterol concentrations (p=0.007) in men. During the follow-up, the AA genotype was associated with an adjusted 2.09-fold risk (95% CI 1.17-3.73, p=0.013) of CVD in men. In the METSIM Study, the association with a history of myocardial infarction was replicated in the subgroup of men with type 2 diabetes.


CONCLUSIONS
We suggest that the variation in the FTO gene may contribute to the development of CVD in men with an abnormal glucose metabolism.
Lappalainen
T
T
School of Public Health and Clinical Nutrition, Department of Clinical Nutrition and Food and Health Research Centre, University of Kuopio, Kuopio, Finland. tiina.lappalainen@uef.fi
Kolehmainen
M
M
Schwab
U S
US
Tolppanen
A M
AM
Stančáková
A
A
Lindström
J
J
Eriksson
J G
JG
Keinänen-Kiukaanniemi
S
S
Aunola
S
S
Ilanne-Parikka
P
P
Herder
C
C
Koenig
W
W
Gylling
H
H
Kolb
H
H
Tuomilehto
J
J
Kuusisto
J
J
Uusitupa
M
M
D000368:Aged; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism*; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D005838:Genotype; D018149:Glucose Intolerance / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors
D001786:Blood Glucose; D011506:Proteins; D002097:C-Reactive Protein; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human