Context:Very recently the unforeseen role of syndecan 3 (SDC3), a family of membrane-bound heparin sulfate proteoglycans, in the regulation of energy balance has been discovered in the Sdc3 null female mice.Objective: The objective of the study was to test the hypothesis that single nucleotide polymorphisms (SNPs) in SDC3 are associated with obesity in the Korean population.Design/Setting/Subjects: We conducted a population-based cohort study consisting of 229 control and 245 study subjects and a second independent study consisting of 192 control and 115 study subjects. Main Outcome Measurement:Body mass index (BMI) was measured.Results: First, Sdc3 mRNA expression in the brain of ob/ob mice was profoundly increased, compared with control mice. Next, all three nonsynonymous SNPs [T271I (rs2282440, CϾT), D245N (rs4949184, CϾT), and V150I (rs2491132, CϾT)] in the SDC3 gene in control female subjects (BMI Ͻ 23, n ϭ 229) and obese female subjects (BMI Ͼ 30, n ϭ 245) were genotyped. We demonstrated the presence of clear ethnic differences in three nonsynonymous SDC3 SNPs among African-Americans, Chinese, Europeans, and Koreans. Of three SNPs in SDC3, rs4949184 was not associated with obesity and the other two SNPs (rs2282440 and rs2491132) were strongly associated with obesity (P Ͻ 0.0001), and the results were confirmed in the second independent study group. Haplotype analysis also revealed strong association with obesity ( 2 ϭ 76.92, P Ͻ 0.000001). Conclusions:There are ethnic differences in the SDC3 polymorphisms, and the polymorphisms are strongly associated with obesity.

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