DNA methylation of <i>SSPN</i> is linked to adipose tissue distribution and glucose metabolism

Abstract

DNA methylation is a crucial epigenetic mechanism in obesity and fat distribution. We explored the Sarcospan ( SSPN) gene locus by using genome-wide data sets comprising methylation and expression data, pyrosequencing analysis in the promoter region, and genetic analysis of an SNP variant rs718314, which was previously reported to associate with waist-to-hip ratio. We found that DNA methylation influences several clinical variables related to fat distribution and glucose metabolism, while SSPN mRNA levels showed directionally opposite effects on these traits. Complete DNA methylation of the SSPN promoter construct suppressed the gene expression of firefly luciferase in MCF7 cells. Moreover, rs718314 was associated with waist and with DNA methylation at CpG sites. Our data strongly support the role of the SSPN locus in body fat composition and glucose homeostasis, and suggest that this is most likely the result of changes in DNA methylation of SSPN in adipose tissue.-Keller, M., Klös, M., Rohde, K., Krüger, J., Kurze, T., Dietrich, A., Schön, M. R., Gärtner, D., Lohmann, T., Dreßler, M., Stumvoll, M., Blüher, M., Kovacs, P., Böttcher, Y. DNA methylation of SSPN is linked to adipose tissue distribution and glucose metabolism.