Exp Clin Endocrinol Diabetes 2006; 114(4): 147-152
DOI: 10.1055/s-2006-924079

J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

The Leu7Pro Polymorphism of Neuropeptide Y is Associated with Younger Age of Onset of Type 2 Diabetes Mellitus and Increased Risk for Nephropathy in Subjects with Diabetic Retinopathy

U. Jaakkola1 , 2 , U. Pesonen1 , E. Vainio-Jylhä3 , M. Koulu1 , M. Pöllönen3 , J. Kallio1 , 4
  • 1Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland
  • 2Department of Ophthalmology, Turku City Hospital, Turku, Finland
  • 3Department of Ophthalmology, Turku University Hospital, Turku, Finland
  • 4Centre of Biotechnology, University of Turku, Turku, Finland
Further Information

Publication History

Received: December 2, 2005 First decision: January 19, 2006

Accepted: January 26, 2006

Publication Date:
17 May 2006 (online)


Known risk factors for diabetic retinopathy and nephropathy are long duration of diabetes, high HbA1 c concentration, high blood pressure, and pregnancy. Retinopathy is also an independent predictor of other diabetic complications, especially in type 1 diabetes patients ([El-Asrar et al., 2001]). Many studies have indicated genetic predisposition for diabetic retinopathy ([Awata et al., 2002]; [Birinci et al., 2002]; [Kumaramanickavel et al., 2001]; [Olmos et al., 2000]; [Ray et al., 2004]; [Taverna et al., 2002]) and nephropathy ([Neugebauer et al., 2000]; [Pettersson-Fernholm et al., 2004]). Two earlier studies have shown that the leucine7 to proline7 (Leu7Pro) polymorphism in prepro-neuropeptide Y is associated with retinopathy ([Koulu et al., 2004]; [Niskanen et al., 2000 b]) and among type 1 diabetes patients with an increased risk for diabetic nephropathy ([Pettersson-Fernholm et al., 2004]). However, the association of this polymorphism with diabetic nephropathy in type 2 diabetic subjects has not been studied yet.

Neuropeptide Y (NPY) is a multifunctional sympathetic transmitter of central and peripheral nervous systems regulating e.g. metabolic balance, vasoconstriction, hormone secretion, and angiogenesis ([Pedrazzini et al., 2003]). It is co-stored and co-released with noradrenalin (NA) during sympathetic stimulation. The Leu7Pro polymorphism in the signal peptide of NPY is relatively common in European populations. In Caucasian populations the carrier frequency of the Pro7 allele is 7 - 12 %, in Brazil it is 5.4 %, and in the Asian and African-American populations the prevalence of the Pro7 allele has been very low (< 0.5 %) ([Ding, 2003]). The polymorphism has been shown to be associated with atherosclerosis and its risk factors in obese, diabetic, and even non-diabetic subjects ([Karvonen et al., 1998]; [Karvonen et al., 2001]; [Niskanen et al., 2000 a]; [Pettersson-Fernholm et al., 2004]).

It has also been demonstrated that the polymorphism is associated with increased formation of mature NPY in cells as well as many functional changes in hormonal and autonomic balance in healthy subjects ([Jaakkola et al., 2005]; [Kallio et al., 2001 a]; [Kallio et al., 2001 b]; [Kallio et al., 2003]). Healthy subjects with the Leu7Pro polymorphism have altered plasma NPY, NA, insulin ([Jaakkola et al., 2005]; [Kallio et al., 2001 a]; [Kallio et al., 2003]) and serum free fatty acid (FFA) concentrations ([Pihlajamaki et al., 2003]), and, during physical exercise, increased GH concentrations ([Kallio et al., 2001 b]). The present study was performed to evaluate the role of the Leu7Pro polymorphism in severity and development of ocular and nephrological complications in patients with diabetes.


MD Ulriikka Jaakkola

Department of Pharmacology, Drug Development and Therapeutics
University of Turku

Itäinen Pitkäkatu 4B

20520 Turku


Phone: + 358-50-5462328

Fax: + 358-2-333 72 16

Email: ulriikka.jaakkola@utu.fi