title: Association of the (AU)AT-rich element polymorphism in PPP1R3 with hormonal and metabolic features of polycystic ovary syndrome.
abstract: Insulin resistance, a key factor in the pathogenesis of polycystic ovary syndrome (PCOS), is associated with a reduction in activation of muscle glycogen synthase. A 5-bp insertion-deletion polymorphism in the (AU)AT-rich element (ARE) within the 3'-untranslated region of the gene encoding the muscle-specific glycogen-targeting subunit of protein phosphatase 1 (PPP1R3) has been associated with insulin resistance and type 2 diabetes. The present study was undertaken to examine the relationship of the ARE polymorphism with clinical and hormonal characteristics of women with PCOS. We studied 186 women with PCOS who had undergone a standard 75-g oral glucose tolerance test and measurement of serum androgen and SHBG levels. Among the largest cohort of nondiabetic subjects (Caucasian, n = 112), the presence of the deletion allele (ARE-2) was associated with insulin resistance and hyperandrogenemia. There was no association of the ARE polymorphism with body mass index or blood glucose concentration during the oral glucose tolerance test. Subjects who were homozygous for the insertion allele (ARE-1/1) had a mean insulin area under the curve (99,116 +/- 6,625 pmol/liter.min) that was significantly lower than that in either the heterozygous (ARE-1/2) (132,195 +/- 12,340 pmol/liter.min) or homozygous (ARE-2/2) (164,661 +/- 24,219 pmol/liter.min) deletion groups. In addition, ARE-1/1 subjects had significantly lower serum concentrations of dehydroepiandrosterone sulfate compared with ARE-2/2 subjects (4.2 +/- 0.3 vs. 6.6 +/- 0.7 micromol/liter) and a trend toward lower levels of free testosterone (78.8 +/- 6.5 vs. 114.1 +/- 30.8 pmol/liter). Studies of diabetic and nondiabetic PCOS women of other racial and ethnic backgrounds will be necessary to assess the impact of this and other variants in PPP1R3 upon the phenotype and natural history of women with PCOS.
authors.affiliation: Department of Biochemistry, The University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Sergio Y
authors.initials: SY
authors.lastname: Alcoser
authors.forename: Manami
authors.initials: M
authors.lastname: Hara
authors.forename: Graeme I
authors.initials: GI
authors.lastname: Bell
authors.forename: David A
authors.initials: DA
authors.lastname: Ehrmann
mesh_terms: D020856:AT Rich Sequence; D000328:Adult; D001741:Black or African American; D001786:Blood Glucose; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism*; D011110:Polymorphism, Genetic; D054645:Protein Phosphatase 1; D044465:White People
chemical_list: D001786:Blood Glucose; D007328:Insulin; C114205:PPP1R3A protein, human; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1