Leucine 7 to proline 7 polymorphism in the neuropeptide Y gene is associated with enhanced carotid atherosclerosis in elderly patients with type 2 diabetes and control subjects.
We have recently demonstrated that subjects having Pro7 in the signal peptide ofneuropeptide Y (NPY) have higher serum cholesterol and apolipoprotein B levels than individuals with wild-type (Leu7Leu7) signal peptide sequence. We investigated the association of Leu7Pro polymorphism with common carotid intima media thickness (IMT) assessed by ultrasonograph in patients with type 2 diabetes (n = 81; 41 men and 40 women; mean age, 67.1 yr) and nondiabetic subjects (n = 105; 48 men and 57 women; mean age, 65.5 yr) and genotyped for the Leu7Pro polymorphism in prepro-NPY. The frequency of Pro7 in prepro-NPY was 9.9% (8 of 81) in diabetic patients and 14.3% (15 of 105) in control subjects (P = 0.360). The mean common carotid IMT was 1.04 +/- 0.02 mm in nondiabetic subjects without the Leu7Pro polymorphism and 1.14 +/- 0.04 mm in nondiabetic subjects with in (P = 0.156) and 1:18 +/- 0.03 and 1.58 +/- 0.21mm in diabetic patients without and with the Leu7Pro polymorphism (P = 0.004), respectively. In the analysis of covariance of the entire group, the mean common carotid IMT was independently associated with the Leu7Pro polymorphism (F = 5.165; P = 0.024) after adjustment for known risk factors. Thus, the presence of the Pro7 substitution in the prepro-NPY associates with increased carotid atherosclerosis.
Niskanen
L
L
Department of Clinical Nutrition, University of Kuopio, Finland. leo.niskanen@kuh.fi
Karvonen
M K
MK
Valve
R
R
Koulu
M
M
Pesonen
U
U
Mercuri
M
M
Rauramaa
R
R
Töyry
J
J
Laakso
M
M
Uusitupa
M I
MI
D000368:Aged; D019943:Amino Acid Substitution; D001161:Arteriosclerosis / Q000235:genetics* / Q000503:physiopathology; D001341:Autonomic Nervous System / Q000503:physiopathology; D001794:Blood Pressure; D016893:Carotid Stenosis / Q000235:genetics* / Q000503:physiopathology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005838:Genotype; D006339:Heart Rate; D006801:Humans; D007930:Leucine; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics*; D011110:Polymorphism, Genetic; D011392:Proline; D012307:Risk Factors
D009478:Neuropeptide Y; D011392:Proline; D007930:Leucine