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Positive Association of Obesity with Single Nucleotide Polymorphisms of Syndecan 3 in the Korean Population

Departments of Biochemistry (E.H., H.H.B.) and Neuropsychiatry (J.W.K.) and Kohwang Medical Research Institute (B.-K.C., S.V.Y., J.-H.C.), College of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea; Department of Obesity Management (M.-J.K.), Graduate School of Obesity Science, Dongduk Women’s University, Seoul 136-714, Republic of Korea; Imagine Obesity Research Institute (J.-J.R., D.-J.O., T.-H.R., K.-H.K.), Seoul 138-170, Republic of Korea; Medical Science Institute (H.J.L.), Kangwon National University, Chunchon 200-170, Republic of Korea; and Department of Preventive Medicine (D.-H.S.), School of Medicine and Institute for Medical Science, Keimyung University, Daegu 704-701, Republic of Korea

Address all correspondence and requests for reprints to: Jong Woo Kim, M.D., Ph.D., Faculty of the Department of Neuropsychiatry, Kyung Hee Medical Center, Kyung Hee University, Hoigi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea. E-mail: eyha{at}khu.ac.kr; psyjongwoo{at}freechal.com.

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, C>T), D245N (rs4949184, C>T), and V150I (rs2491132, C>T)] in the SDC3 gene in control female subjects (BMI < 23, n = 229) and obese female subjects (BMI > 30, n = 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 < 0.0001), and the results were confirmed in the second independent study group. Haplotype analysis also revealed strong association with obesity (² = 76.92, P < 0.000001).

Conclusions: There are ethnic differences in the SDC3 polymorphisms, and the polymorphisms are strongly associated with obesity.