title: Sex hormone-binding globulin genetic variation: associations with type 2 diabetes mellitus and polycystic ovary syndrome.
abstract: Sex hormone-binding globulin (SHBG) is the primary plasma transport protein for sex steroid hormones and regulates the bioavailability of these hormones to target tissues. The gene encoding SHBG is complex and any of several polymorphisms in SHBG have been associated with alterations in circulating SHBG levels. Epidemiological studies have revealed that low plasma SHBG levels are an early indicator of insulin resistance and predict the development of type 2 diabetes mellitus (T2DM) in both men and women. Although associations between low SHBG levels and risk of diabetes could be explained by the observation that elevations in insulin suppress hepatic SHBG production, recent studies documenting that the transmission of SHBG-altering polymorphisms are associated with risk of T2DM suggest that SHBG may have a more direct physiologic role in glucose homeostasis. However, the exact mechanism(s) underlying this association is not known. Non-diabetic women with the polycystic ovary syndrome (PCOS), a common endocrine disorder that is associated with insulin resistance, similarly demonstrate lower levels of SHBG. In light of studies investigating polymorphisms in SHBG and T2DM, our group and others have hypothesized that SHBG may represent a candidate gene for PCOS. In this manuscript, we review studies investigating the association between SHBG polymorphisms and PCOS. In summary, multiple studies in women with PCOS confirm that certain genetic polymorphisms are associated with circulating SHBG levels, but they are not consistently associated with PCOS per se.
authors.affiliation: Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Smothers
authors.forename: A
authors.initials: A
authors.lastname: Lange
authors.forename: J E
authors.initials: JE
authors.lastname: Nestler
authors.forename: J F
authors.initials: JF
authors.lastname: Strauss Iii
authors.forename: E P
authors.initials: EP
authors.lastname: Wickham Iii
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics; D005260:Female; D006801:Humans; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance / Q000235:genetics; D008099:Liver / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D012737:Sex Factors; D012738:Sex Hormone-Binding Globulin / Q000235:genetics* / Q000502:physiology
chemical_list: D007328:Insulin; D020033:Protein Isoforms; D012738:Sex Hormone-Binding Globulin