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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 Subjects¹

Departments of Clinical Nutrition (L.N., R.V., M.I.J.U.), Medicine (L.N., M.L.), and Physiology (R.R., J.T.), University of Kuopio, and Kuopio Research Institute of Exercise Medicine and Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital (R.R., J.T.), FIN-70211 Kuopio, Finland; Department of Pharmacology and Clinical Pharmacology, University of Turku (M.K.K., M.K., U.P.), FIN-20520 Turku, Finland; and Department of Endocrinology and Metabolism, Merck Research Laboratories, Merck & Co., Inc. (M.M.), Rahway, New Jersey 07065-0900

Address all correspondence and requests for reprints to: Leo Niskanen, M.D., Department of Medicine, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland. E-mail: leo.niskanen{at}kuh.fi

We have recently demonstrated that subjects having Pro⁷ in the signal peptide of neuropeptide 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 ± 0.21 mm 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.

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