OBJECTIVE: Neuropeptide Y is a potent vasoconstrictor thought to enhance the development of atherosclerosis. The leucine 7 to proline 7 (Leu7Pro) polymorphism, located in the signal peptide part of the human preproneuropeptide Y, has been associated with serum lipid levels, intima-media thickness of the common carotid arteries, and diabetic retinopathy in type 2 diabetic patients. Therefore, we investigated the impact of the Leu7Pro polymorphism on diabetic nephropathy, cardiovascular risk factors, and cardiovascular disease in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 996 patients from the Finnish Diabetic Nephropathy study were studied in a case-control, cross-sectional study. The carrier frequency of the Pro7 substitution was 13% in the entire study population. RESULTS: The Pro7 substitution was more common in patients with proteinuria than in those with a normal albumin excretion rate (16 vs. 11%, P < 0.05). Patients with the Pro7 allele had worse glycemic control (HbA(1c) 8.8 vs. 8.5%, P < 0.005), more coronary heart disease (CHD) (14 vs. 8%, P < 0.05), and higher serum triglycerides (1.65 vs. 1.35 mmol/l, P < 0.005) than patients with the wild-type genotype. There were no differences in the plasma neuropeptide Y levels between the patients with Pro7 compared with those with the wild-type genotype. The Leu7Pro polymorphism was independently associated with HbA(1c) (P < 0.001), proteinuria (P < 0.01), and CHD (P < 0.01) in multiple regression analyses. CONCLUSIONS: We conclude that the Leu7Pro polymorphism may contribute to the genetic susceptibility to diabetic nephropathy and CHD in type 1 diabetic patients, possibly by influencing glycemic control and triglycerides.
OBJECTIVE: Neuropeptide Y is a potent vasoconstrictor thought to enhance the development of atherosclerosis. The leucine 7 to proline 7 (Leu7Pro) polymorphism, located in the signal peptide part of the human preproneuropeptide Y, has been associated with serum lipid levels, intima-media thickness of the common carotid arteries, and diabetic retinopathy in type 2 diabeticpatients. Therefore, we investigated the impact of the Leu7Pro polymorphism on diabetic nephropathy, cardiovascular risk factors, and cardiovascular disease in type 1 diabeticpatients. RESEARCH DESIGN AND METHODS: A total of 996 patients from the Finnish Diabetic Nephropathy study were studied in a case-control, cross-sectional study. The carrier frequency of the Pro7 substitution was 13% in the entire study population. RESULTS: The Pro7 substitution was more common in patients with proteinuria than in those with a normal albumin excretion rate (16 vs. 11%, P < 0.05). Patients with the Pro7 allele had worse glycemic control (HbA(1c) 8.8 vs. 8.5%, P < 0.005), more coronary heart disease (CHD) (14 vs. 8%, P < 0.05), and higher serum triglycerides (1.65 vs. 1.35 mmol/l, P < 0.005) than patients with the wild-type genotype. There were no differences in the plasma neuropeptide Y levels between the patients with Pro7 compared with those with the wild-type genotype. The Leu7Pro polymorphism was independently associated with HbA(1c) (P < 0.001), proteinuria (P < 0.01), and CHD (P < 0.01) in multiple regression analyses. CONCLUSIONS: We conclude that the Leu7Pro polymorphism may contribute to the genetic susceptibility to diabetic nephropathy and CHD in type 1 diabeticpatients, possibly by influencing glycemic control and triglycerides.
Authors: L V K S Bhaskar; K Thangaraj; Anish M Shah; G Pardhasaradhi; K Praveen Kumar; A G Reddy; A Papa Rao; C J Mulligan; Lalji Singh; V R Rao Journal: J Hum Genet Date: 2007-06-07 Impact factor: 3.172
Authors: Roma Patel; Mitesh Dwivedi; Mohmmad Shoab Mansuri; Naresh C Laddha; Ami Thakker; A V Ramachandran; Rasheedunnisa Begum Journal: PLoS One Date: 2016-10-17 Impact factor: 3.240
Authors: Stephan Schiekofer; Marcus E Kleber; Winfried Maerz; Franz M Rasche; Jochen G Schneider Journal: Int J Endocrinol Date: 2017-05-30 Impact factor: 3.257
Authors: Svati H Shah; Neil J Freedman; Lisheng Zhang; David R Crosslin; David H Stone; Carol Haynes; Jessica Johnson; Sarah Nelson; Liyong Wang; Jessica J Connelly; Michael Muehlbauer; Geoffrey S Ginsburg; David C Crossman; Christopher J H Jones; Jeffery Vance; Michael H Sketch; Christopher B Granger; Christopher B Newgard; Simon G Gregory; Pascal J Goldschmidt-Clermont; William E Kraus; Elizabeth R Hauser Journal: PLoS Genet Date: 2009-01-02 Impact factor: 5.917