Leucine7 to proline7 polymorphism in the preproneuropeptide Y is associated with the progression of carotid atherosclerosis, blood pressure and serumlipids in Finnish men

A rather common leucine7-to-proline7 (Leu7Pro) polymorphism in the preprone uropeptide Y (prepro-NPY) gene signal peptide may be important in blood pre ssure regulation, cholesterol metabolism and the pathogenesis of atheroscle rosis in humans. We examined the associations of the Leu7Pro polymorphism w ith carotid atherosclerotic progression, blood pressure and serum lipids in a population-based sample of 966 men aged 42-60 years in Finland. The Pro7 substitution (carrier frequency 12.2%) was associated with accelerated fou r-year increase in the mean (P = 0.01) and maximal (P = 0.007) common carot id intima-media thickness (IMT) and with slightly increased systolic (P = 0 .03) and diastolic (P = 0.02) blood pressures, adjusted for other major ris k factors. Men with Pro7 substitution had 30.6% (95% Cl 6.9-54.0%) greater increase in the mean IMT and 20.0% (95% CI 5.3-34.4%) greater increase in t he maximal IMT than men with Leu7/Leu7 genotype. The Pro7 substitution was also related to increased serum total cholesterol (P = 0.01) and LDL choles terol (P = 0.02) in obese (body mass index (BMI) > 30 kg/m(2)) men. This st udy provides important evidence suggesting that the Pro7 substitution in th e prepro-NPY is an important risk factor for accelerated atherosclerotic pr ogression, increased blood pressure and increased serum cholesterol in huma ns. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.