Role of syndecan-3 polymorphisms in obesity and female hyperandrogenism

The heparan sulfate proteoglycan syndecan-3 (SDC3) is a novel regulator of feeding behavior and body weight. Recently, an association of SDC3 polymorphisms with obesity has been observed in Koreans. As female obesity is associated with hyperandrogenism and infertility, we studied the role of SDC3 polymorphisms in female individuals undergoing diagnostics prior to infertility treatment. For this purpose, endocrine parameters and body mass index of 249 women were assessed. Genotyping of V208I, D303N, and T329I was performed with TaqMan technology using lymphocyte-derived DNA and allelic discrimination polymerase chain reaction. Chi-square test, Student's t test, and one-way analysis of variance were used for statistical analysis. We find that an infrequent genotype and allele variation of T329I correlated with obesity (p = 0.028). Genotype and alleles of V208I were associated with luteinizing hormone (p = 0.007 and p = 0.001, respectively), luteinizing hormone/follicle-stimulating hormone (p = 0.002 and p < 0.005, respectively), 17 hydroxyprogesterone (p = 0.007 and p = 0.001, respectively), androstenedione (p = 0.046 and p = 0.013, respectively), and sex hormone-binding globulin (p = 0.021). We conclude that marked ethnic differences of the SDC3 SNP distribution in our European population could account for correlations less predominant compared to Koreans. While infrequent variations of T329I correlated with obesity, V208I was associated with endocrine parameters related to hyperandrogenism. These findings indicate that SDC3 polymorphisms could contribute to the link between female hyperandrogenism and obesity and suggest a novel potential role for SDC3 as a modulator of gonadal steroid function.