cell biochemistry and function Cell Biochem Funct 2006; 24: 261–267. Published online 22 March 2005 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1027/cbf.1218 Apolipoprotein B gene variants are involved in the determination of blood glucose and lipid levels in patients with non-insulin dependent diabetes mellitus Belgin Su ¨sleyici Duman 1 , Melek O ¨ ztu ¨rk* 2 , Selma Ylmazer 2 , Penbe C ¸ ag ˘atay 3 and Hu ¨srev Hatemi 4,5 1 Kadir Has University, Faculty of Medicine, Medical Biology and Genetics Department, _ Istanbul, Turkey 2 Istanbul University, Cerrahpasa Faculty of Medicine, Medical Biology Department, _ Istanbul, Turkey 3 Istanbul University, Cerrahpasa Faculty of Medicine, Biostatistics Department, _ Istanbul, Turkey 4 Turkish Diabetes Hospital, Dr Celal Oker Street. No. 10 Harbiye, _ Istanbul, Turkey 5 Istanbul University, Cerrahpasa Faculty of Medicine, Endocrinology and Metabolism Department, _ Istanbul, Turkey We have examined the frequency of the EcoRI, XbaI and MspI RFLPs of the apolipoprotein B (apo B) gene in 110 type 2 diabetic patients and 91 healthy control subjects in order to ascertain whether variation in this gene may influence the devel- opment of non-insulin dependent diabetes mellitus (type 2 diabetes). Serum lipids including total-cholesterol (T-Chol), tria- cylglycerol (TAG), apolipoprotein E (apo E), apolipoprotein AI (apo AI), apolipoprotein B and lipoprotein (a) (Lp(a)) were analysed. Genomic DNA was extracted and the apo B polymorphic regions amplified by the polymerase chain reaction. Regions carrying EcoRI, XbaI, and MspI restriction sites present in the apo B gene were amplified and digested separately by the respective enzymes. No significant difference for genotypic frequencies was observed for the EcoRI, XbaI and MspI restriction sites in type 2 diabetic patients as compared to controls. Type 2 diabetic patients and controls with EcoRI þ/þ and XbaI þ/þ genotypes had higher apo E levels. The MspI þ/þ genotype is more frequent in the patient and control groups with elevated T-Chol. Furthermore, the EcoRI /, XbaI /, and MspI þ/þ genotypes were found to be significantly more frequent in type 2 diabetic patients with higher blood glucose levels. This study identifies the apo B gene polymorph- isms in modulating plasma lipid/lipoprotein and glucose levels in patients with type 2 diabetes. Copyright # 2005 John Wiley & Sons, Ltd. key words — non-insulin dependent diabetes mellitus; apolipoprotein B; polymorphism INTRODUCTION Type 2 diabetes mellitus is a heterogeneous disorder that develops in response to both genetic and environ- mental factors. 1–5 The predisposition to type 2 dia- betes is thought to be conferred by a number of different genes that in isolation may have only minor effects, but in combination lead to the characteristic pathophysiological condition. 6 This genetic suscept- ibility may be preferentially conferred by an unfa- vourable combination of individual polymorphisms in the genes involved, each one controlling part of the pathogenic process. 7 Apolipoprotein B is a major protein component of low density lipoprotein (LDL). Apo B plays a central role in lipoprotein metabolism through regulation of total cholesterol (T-Chol) and LDL concentrations in plasma. This regulation is mediated by binding of apo B, present in LDL, to LDL receptors (LDLR) on the cell surface. 8 Genetic polymorphisms of apo B have been shown to have a significant effect on plasma lipid levels and have been associated with type 2 diabetes in some studies. 9,10 Diabetic dyslipidemia comprises multiple lipoprotein disorders. The most typical find- ings are high triacylglycerol (TAG) concentrations, low levels of high density lipoprotein-cholesterol (HDL-Chol) and normal or slightly increased Received 29 September 2004 Revised 14 October 2004 Copyright # 2005 John Wiley & Sons, Ltd. Accepted 9 November 2004 * Correspondence to: Professor Melek O ¨ ztu ¨rk, _ Istanbul University, Cerrahpasa Faculty of Medicine, Medical Biology Department Cerrahpas ¸a, _ Istanbul, Turkey. Tel: 00 90 532 442 48 34. Fax:00 90 212 632 00 50. E-mail: ozturkmel@superonline.com