Article 1 Sramkova D et al. The UCP1 A-3826G Polymorphism in Czech Population … Exp Clin Endocrinol Diabetes 2007; 115: 1–5 ECED/762/23.4.2007/Macmillan received . .  first decision . .  accepted . .  Bibliography DOI 10.1055/s-2007-977732 Exp Clin Endocrinol Diabetes 2007; 115: 1–5 © J. A. Barth Verlag in Georg Thieme Verlag KG · Stuttgart · New York · ISSN 0947-7349 Correspondence D. Sramkova Institute of Endocrinology 116 94 Narodni 8 Prague 1 Tel.: + 420/224/90 53 01 Fax: + 420/224/90 53 25 dsramkova@endo.cz Key words   type 2 diabetes mellitus   uncoupling protein 1   A-3826G polymorphism   insulin sensitivity   obesity in humans The UCP1 Gene Polymorphism A-3826G in Relation to DM2 and Body Composition in Czech Population ing the electrochemical gradient over the inner mitochondrial membrane, UCP1 uncouples oxi- dative phosphorylation, which leads to the pro- duction of heat instead of energy storage in the form of ATP (Klingenberg et al., 1990). The ther- mogenic function of brown fat tissue is under the control of catecholamines acting through adreno- receptors. As a consequence of norepinephrine binding to the adipocyte plasma membrane, lipolysis is stimulated and non-esterified fatty acids are released. These fatty acids serve as a substrate in the process of brown fat thermogen- esis, but they also act as the cytosolic second messengers activating UCP1 (Locke et al., 1982). Although a controversy exists concerning the physiological significance of brown adipose tis- sue in adults and its possible contribution to body weight control, genetic analysis of various human cohorts suggested a participation of UCP1 in fat tissue content regulation (Fumeron et al., 1996; Heilbronn et al., 2000; Clement et al., 1996; Oppert et al., 1994; Esterbauer et al., 1998). There is a large amount of evidence that brown adi- Abbreviations & UCP uncoupling protein DM2 type 2 diabetes mellitus BMI body mass index WHR waist to hip ratio WHeR waist to height ratio DI disposition index G 0 fasting serum blood glucose I 0 fasting serum insulin oGTT oral glucose tolerance test ivITT intravenous insulin tolerance test PCR polymerase chain reaction RFLP restriction fragment length polymor- phism. Introduction & The gene for mitochondrial uncoupling protein 1 (UCP1) is expressed in brown fat (Cinti et al., 1989). It belongs to the family of mitochondrial carrier proteins (Cassard et al., 1990). By decreas- Authors D. Sramkova, S. Krejbichova, J. Vcelak, M. Vankova, P. Samalikova, M. Hill, H. Kvasnickova, K. Dvorakova, K. Vondra, V. Hainer, B. Bendlova Affiliation Institute of Endocrinology, Prague, Czech Republic Abstract & Mitochondrial uncoupling contributes to the control of energy expenditure. The brown fat specific uncoupling protein 1 (UCP1) mRNA was detected in intraperitoneal and extraperitoneal adipose tissue in adult humans. The A-3826G polymorphism in the UCP1 gene promoter region was found to be associated with reduced mRNA expression indicating that the polymorphism is of functional importance. Objective: To determine allelic frequencies and genotypic distribution of the A-3826G poly- morphism and to study its possible association with anthropometric parameters and biochemi- cal markers of glucose and lipid metabolism in type 2 diabetes mellitus (DM2) patients (n = 295), in offsprings of DM2 patients (n = 113), and in healthy adults without family history of DM2 (n = 120). Results and Discussion: In the whole cohort of 528 subjects, the G allele was observed with a frequency of 0.26. Genotypic distribution did not differ between diabetics and controls. However, in the offsprings of DM2 patients, significantly higher BMI and a trend towards higher waist to hip ratio, waist to height ratio, waist circumfer- ence, and subcutaneous fat mass was observed in the AG genotype compared with the wild- type. Similar tendency was evident in the control group. This indicates possible involvement of the A-3826G polymorphism in the regulation of body composition.