title: Association between serum levels and pentanucleotide polymorphism in the sex hormone binding globulin gene and cardiovascular risk factors in females with polycystic ovary syndrome.
abstract: The objective of the present study was to evaluate the influence of TAAAA repeat allele length on the levels of serum sex hormone binding globulin (SHBG) and cardiovascular risk factors in patients with polycystic ovary syndrome (PCOS). The study included 91 females with PCOS and 99 healthy controls. Phenotypic hyperandrogenism, body mass index and waist‑to‑hip ratio (WHR) were recorded. Hormonal profiles, fasting insulin and glucose levels, lipid profiles and C‑reactive protein (CRP) levels were measured. Genotyping of TAAAA repeat polymorphisms in the SHBG gene was performed. No significant difference was found in the frequency and distribution of TAAAA repeat alleles between PCOS patients and controls (P=0.739). In PCOS patients, SHBG levels were inversely correlated with serum C‑reactive protein (CRP) levels (R=-0.489, P<0.001). PCOS patients with long TAAAA repeat alleles had significantly lower serum SHBG and free testosterone levels, yet higher CRP levels than patients with short allele repeats. A multiple linear regression model using the number of TAAAA repeats, waist‑to‑hip ratio, a homeostatic model assessment of insulin resistance and age as independent predictors explained 44.8% of the variability in serum SHBG levels. In this model, TAAAA repeat polymorphism was found to be the only reliable predictor of serum SHBG levels (P<0.001). In conclusion, the TAAAA repeat polymorphism was shown to not be a major determinant of the PCOS status, although it influenced serum SHBG levels in females with PCOS. A strong independent association existed between serum SHBG and CRP levels. CRP is an established risk factor of cardiovascular disease and a marker of low‑grade inflammation, typical of atherogenesis. This may be one of the pathways by which low SHBG levels affect cardiovascular risk.
authors.affiliation: Department of Obstetrics and Gynecology, University of Zagreb Medical School, Division of Human Reproduction, University Medical Centre Zagreb, 10000 Zagreb, Croatia.
authors.forename: Dinka Pavicic
authors.initials: DP
authors.lastname: Baldani
authors.affiliation: Department of Obstetrics and Gynecology, University of Zagreb Medical School, Division of Human Reproduction, University Medical Centre Zagreb, 10000 Zagreb, Croatia.
authors.forename: Lana
authors.initials: L
authors.lastname: Skrgatic
authors.affiliation: Department of Obstetrics and Gynecology, University Medical Centre Ljubljana, Ljubljana SI‑1000, Slovenia.
authors.forename: Jasmina Ziva
authors.initials: JZ
authors.lastname: Cerne
authors.affiliation: Clinical Institute of Laboratory Diagnostics, University Medical Centre Zagreb, 10000 Zagreb, Croatia.
authors.forename: Sasa Kralik
authors.initials: SK
authors.lastname: Oguic
authors.affiliation: Faculty of Medicine, University of Ljubljana, Ljubljana SI‑1104, Slovenia.
authors.forename: Blaz Matija
authors.initials: BM
authors.lastname: Gersak
authors.affiliation: Department of Obstetrics and Gynecology, University Medical Centre Ljubljana, Ljubljana SI‑1000, Slovenia.
authors.forename: Ksenija
authors.initials: K
authors.lastname: Gersak
mesh_terms: D000328:Adult; D000483:Alleles; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D009841:Oligonucleotides / Q000235:genetics*; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D009841:Oligonucleotides; D012738:Sex Hormone-Binding Globulin; D002097:C-Reactive Protein