Leu7Pro Polymorphism in the Neuropeptide Y (NPY) Gene is Associated with Impaired Glucose Tolerance and Type 2 Diabetes in Swedish Men

S. Nordman; B. Ding; C.-G. Östenson; L. Kärvestedt; K. Brismar; S. Efendic; H. F. Gu

doi:10.1055/s-2005-865650

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2005; 113(5): 282-287
DOI: 10.1055/s-2005-865650

Article

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

Leu7Pro Polymorphism in the Neuropeptide Y (NPY) Gene is Associated with Impaired Glucose Tolerance and Type 2 Diabetes in Swedish Men

S. Nordman¹ , B. Ding² , C.-G. Östenson¹ , L. Kärvestedt³ , K. Brismar¹ , S. Efendic¹ , H. F. Gu¹

¹Diabetes Center Karolinska, Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden
²Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
³Stockholm Hospital, Stockholm, Sweden

Abstract

The neuropeptide Y (NPY) is a neuropeptide with a role in the regulation of satiety and energy balance of body weight, insulin release, cardiovascular and central endocrine systems. In order to evaluate whether the NPY gene variations contribute to development of type 2 diabetes (T2DM), we have performed a genetic association study for Leu7Pro (T1128 C) polymorphism of the NPY gene in impaired glucose tolerance (IGT) and T2DM. Genotyping experiments for this non-synonymous single nucleotide polymorphism (SNP) in 263 patients with T2DM, 309 subjects with IGT and 469 non-diabetic healthy individuals in Swedish Caucasians were performed by using Dynamic Allele Specific Hybridisation (DASH). We found that the frequencies of the “risk” allele C in the subjects with IGT and the patients with T2DM in Swedish men were 13 % (p = 0.002, OR = 3.70, 1.65 - 8.29 95 % CI) and 10 % (p = 0.007, OR = 4.80, 1.47 - 11.33 95 % CI) respectively, which were significantly higher than the C allele frequency in non-diabetic controls (6 %). Furthermore, we found that the carriers with TC and CC genotypes in the subjects with IGT in Swedish men had significantly higher fasting plasma glucose in comparison with the TT carriers (5.6 ± 0.7 mmol/l vs. 5.2 ± 0.7 mmol/l, p = 0.021). The present study thus provides the evidence that Leu7Pro polymorphism in the NPY gene is associated with IGT and T2DM in Swedish men, and indicates that the NPY gene variations contribute to development of T2DM. Questions of gender specificity may be explained by genetic backgrounds, sense of coherence for stress and other factors in environment.

Key words

Neuropeptide Y - type 2 diabetes - impaired glucose tolerance - single nucleotide polymorphism - genetic association

Full Text

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Harvest F. Gu

L6:B2, Diabetes Center Karolinska, Department of Molecular Medicine, Karolinska Hospital

Stockholm, 171 76

Sweden

Phone: + 46851779515

Fax: + 46 8 51 77 36 58

Email: harvest.gu@molmed.ki.se