PCOS – polycystic ovary syndrome; SNP – single nucleotide polymorphism; SHBG – gender hormones-binding globulin; T2DM – Diabetes mellitus
Despite uncertainty regarding specific metabolic pathways through which SHBG influences insulin sensitivity and the risk of T2DM, SHBG has been proposed as an attractive candidate gene for PCOS (67;68). Specifically, our group and others have hypothesized that genetic variation in SHBG levels may contribute to at least two of metabolic derangements that are central to the disorder, namely insulin resistance and hyperandrogenemia. n repeat polymorphism, rs1799941 (?67G>A in the 5? untranslated region), rs6257 (IVS1-17T>C); rs6259 (Ex8 +6G>A(D356N)) and rs727428 (1121bp 3?of STP T>C) ( Figure 2 ).
Rectangles represent exons (E). Black diamonds represent coding SNPs; gray diamonds represent 5?-UTR SNP; unfilled diamonds represents intronic SNPs; triangles represents promoter SNP. Numbers refer to relativepositions along chromosome 17. PL – SHBG gene downstream promoter; PT – SHBG gene upstream promoter. (TAAAA)n is associated with SHBG levels and PCOS. rs1799941 is associated with SHBG levels, androgen levels and risk of T2DM. rs6257 is associated with SHBG levels and risk of T2DM. rs6259 is associated with SHBG levels and risk of T2DM. rs727428 is associated with SHBG levels. Adapted from Xita N, Tsatsoulis A. Molecular and Cellular Endocrinology. 2010;–65.
P156L is actually associated with the really lowest SHBG profile and big hyperandrogenism
Polymorphisms in a pentanucleotide (TAAAA)n repeat located in the 5? promoter region of SHBG have been associated with transcriptional activity of the gene in vitro (69). In the general population, the SHBG gene contains at least 6–10 TAAAA repeat, and SHBG transcriptional activity is lower in HepG2 cell lines transfected with SHBG promoter transcripts containing six TAAAA repeats compared with cells containing 7–10 repeats (69). Lees verder