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To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1399-0004.2008.01033.x Byline: HR Han (a), C Shin (e,f), HD Shin (g,h), K Kimm (a), H-L Kim (a), B Oh (a,i), KS Park (b,c), H-J Ryu (a), HS Cha (a), MJ Go (a), Y Ahn (a), BK Koo (b,c), YM Cho (b,c), HK Lee (b,c), NH Cho (d) Keywords: BMI; LEP; LEPR; metabolic trait; replication; type 2 diabetes mellitus Abstract: Type 2 diabetes mellitus (T2DM) is a metabolic disorder that is characterized by insulin resistance and hyperglycemia. Leptin inhibits the glucose-stimulated insulin secretion, and leptin receptors are present on [beta] cells as well as on fat cells, thus enabling leptin to modulate both insulin secretion and action. Therefore, leptin (LEP) and leptin receptor (LEPR) genes could play a role in the regulation of glucose and insulin after an oral glucose load. For the association study of LEP and LEPR with T2DM and metabolic traits, 752 women from Seoul National University Hospital (SNUH data) and 532 women from the Korean Health and Genome Study (KHGS data) were selected. Using the SNUH data, we identified that LEP-632G>A and +4998A>C polymorphisms were marginally associated with T2DM, LEP+4950G>A was significantly associated with several metabolic traits, and LEPR+5193G>A, +7187A>C, +27265G>A, +35861T>C, and +52289A>G showed strongly significant association with body mass index (BMI). We observed reproducibility of these results using the KHGS data; LEP+4950G>A and +4998A>C were significantly associated with systolic blood pressure and low-density lipoprotein cholesterol level, respectively. In conclusion, we observed that several polymorphisms in LEPR that had previous reports of association with BMI were significantly replicated in our samples and newly found that some variations of LEP were associated with T2DM and metabolic traits. Author Affiliation: (a)Center for Genome Science, National Institute of Health, Seoul, Korea (b)Genome Research Center for Diabetes and Endocrine Disease, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea (c)Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea (d)Department of Preventive Medicine, Ajou University School of Medicine, Suwon, Korea (e)Institute of Human Genomic Study, Korea University Medical Science Research Center, Seoul, Korea (f)Department of Internal Medicine, Korea University Ansan Hospital, Gyeonggi-do, Korea (g)Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul, Korea (h)Department of Life Science, Sogang University, Seoul, Korea (i)Department of Biomedical Engineering, School of Medicine, Kyung Hee University, Seoul, Korea Article History: Received 1 January 2008, revised and accepted for publication 10 April 2008 Article note: Bermseok Oh, PhD, Department of Biomedical Engineering, School of Medicine, Kyung Hee University, 1 Hoeki-dong, Dongdaemun-gu, Seoul 130-702, Korea., Tel.: +82 2 961-0290; fax: +82 2 961-5515; e-mail: ohbs@khu.ac.kr Kyong Soo Park, MD, PhD, Department of Internal Medicine, Seoul National University, College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744, Korea., Tel.: +82 2 2072 1789; fax: +82 2 3676 8309; e-mail: kspark@snu.ac.kr