Conversely, sRAGE [74], Mn-SOD [51,75] BMP6, and GDF2 [76] were downregulated in the overweight/obese PCOS cohort and all of these were reported to have reduced expression in obesity with metabolic syndrome; it is therefore not surprising that the levels of these proteins were reduced in the overweight/ obese subset of women, both with and without PCOS, though it appears that PCOS caused further downregulation. This evidence concerns the gene GDF2 and obesity due to melanocortin 4 receptor deficiency.