The Leu7Pro polymorphism of the signal peptide of neuropeptide Y (NPY) gene is associated with increased levels of inflammatory markers preceding vascular complications in patients with type 2 diabetes.
OBJECTIVE
The Leucine7 to Proline7 (Leu7Pro) polymorphism of the signal peptide of neuropeptide Y (NPY) increases risk for vascular complications in diabetes. Diabetes is associated with low-grade inflammation, which has an important role in the development of atherosclerosis. Currently, we followed diabetes patients to investigate, if the Pro7 allele is associated with the inflammation related to atherosclerosis.


METHODS
In the 5-year follow-up, the genotyped, pair-matched type 2 diabetes patients (12 with the Pro7 allele and 19 without) were investigated using non-invasive ultrasound based methods to measure the development of atherosclerosis (intima media thickness=IMT) and endothelium-dependent (FMD) and -independent nitrate-mediated (NMD) vasodilatation. The development of diabetic complications was followed annually, and the concentrations of inflammatory markers and NPY in plasma were determined.


RESULTS
Patients with the Pro7 had increased U-albumin/creatinine (p=0.037), E-selectin (p=0.016), fasting insulin (p=0.011) and HOMA index (p=0.013) but decreased serum amyloid P concentrations (p=0.021). Furthermore, men with the Pro7 had increased CRP (p=0.010) and NPY (p=0.026) concentrations. IMT and FMD were similar in all patients, however, NMD decreased more during the follow-up in the patients with the Pro7 (p=0.002). NPY correlated positively with bIMT [r 0.04 (SE 0.02), p=0.007] and E-selectin negatively with FMD [r -0.05 (S.E 0.02), p=0.039].


CONCLUSIONS
Diabetes patients with the Pro7 allele display increased levels of inflammatory molecules and NPY in blood, preceding vascular wall thickening and impaired endothelial dilatation, especially in male patients.
Jaakkola
U
U
Centre for Biotechnology, University of Turku, Tykistökatu 6, Turku, Finland. ulriikka.jaakkola@utu.fi
Kakko
T
T
Seppälä
H
H
Vainio-Jylhä
E
E
Vahlberg
T
T
Raitakari
O T
OT
Kallio
J
J
D000368:Aged; D000419:Albuminuria / Q000235:genetics / Q000276:immunology; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002097:C-Reactive Protein / Q000378:metabolism; D003404:Creatinine / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics* / Q000276:immunology; D003925:Diabetic Angiopathies / Q000000981:diagnostic imaging / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D019040:E-Selectin / Q000097:blood; D005260:Female; D005387:Finland; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D007333:Insulin Resistance; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D009478:Neuropeptide Y / Q000097:blood / Q000235:genetics*; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011110:Polymorphism, Genetic; D021382:Protein Sorting Signals / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D000683:Serum Amyloid P-Component / Q000378:metabolism; D012737:Sex Factors; D013997:Time Factors; D014463:Ultrasonography; D015854:Up-Regulation; D014664:Vasodilation
D015415:Biomarkers; D019040:E-Selectin; D018836:Inflammation Mediators; D009478:Neuropeptide Y; D017395:Plasminogen Activator Inhibitor 1; D021382:Protein Sorting Signals; C051321:SERPINE1 protein, human; D000683:Serum Amyloid P-Component; D002097:C-Reactive Protein; D003404:Creatinine