Neuropeptide Y polymorphism significantly magnifies diabetes and cardiovascular disease risk in obesity: the Hoorn Study.
The leucine7 to proline7 (Leu7Pro) polymorphism in preproneuropeptide Y (preproNPY) has been associated with accelerated atherosclerosis and type II diabetes, both of which are obesity-related diseases. The current study evaluated the impact of obesity on the disease risk linked to the Leu7Pro polymorphism of preproNPY in 393 elderly subjects. In 6 years follow-up, the polymorphism alone did not change the risk for abnormal glucose regulation, while obesity was associated with a significant 3-fold risk (odds ratio (OR) 2.95; 95% confidence interval (CI) 1.81-4.81, P<0.001) and the Leu7Pro polymorphism-obesity interaction, with a remarkable 12-fold risk (OR 12.33; 95% CI 1.18-128.35, P<0.05). The Leu7Pro polymorphism modified significantly the 10-year incidence of cardiovascular events, causing a 7.6-fold increase in the hazard ratio (HR 7.58; 95% CI 2.87-20.03, P<0.001) in the obese but not in the nonobese subjects. The results indicate that obesity may be a pivotal factor in multiplying the disease risk associated with the Leu7Pro polymorphism in preproNPY.
EMGO Institute, VU University Medical Center, Amsterdam, The Netherlands. ulriikka.jaakkola@utu.fi
U
U
Jaakkola
J
J
Kallio
R J
RJ
Heine
G
G
Nijpels
L M
LM
T' Hart
J A
JA
Maassen
L M
LM
Bouter
C D A
CD
Stehouwer
J M
JM
Dekker
D000368:Aged; D001786:Blood Glucose / Q000235:genetics / Q000378:metabolism*; D001794:Blood Pressure / Q000235:genetics; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics; D002318:Cardiovascular Diseases / Q000235:genetics*; D003920:Diabetes Mellitus / Q000209:etiology / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005951:Glucose Tolerance Test; D006801:Humans; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics*; D009765:Obesity / Q000150:complications* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D001786:Blood Glucose; D009478:Neuropeptide Y