Baldani Dinka Pavicic, Skrgatic Lana, Cerne Jasmina Ziva, Oguic Sasa Kralik, Gersak Blaz Matija, Gersak Ksenija
Department of Obstetrics and Gynecology, University of Zagreb Medical School, Division of Human Reproduction, University Medical Centre Zagreb, 10000 Zagreb, Croatia.
Department of Obstetrics and Gynecology, University Medical Centre Ljubljana, Ljubljana SI‑1000, Slovenia.
Mol Med Rep. 2015 May;11(5):3941-7. doi: 10.3892/mmr.2014.3117. Epub 2014 Dec 19.
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.
本研究的目的是评估多囊卵巢综合征(PCOS)患者中TAAAA重复等位基因长度对血清性激素结合球蛋白(SHBG)水平和心血管危险因素的影响。该研究纳入了91名PCOS女性和99名健康对照者。记录了表型高雄激素血症、体重指数和腰臀比(WHR)。测量了激素谱、空腹胰岛素和血糖水平、血脂谱以及C反应蛋白(CRP)水平。对SHBG基因中的TAAAA重复多态性进行了基因分型。PCOS患者和对照组之间TAAAA重复等位基因的频率和分布没有显著差异(P = 0.739)。在PCOS患者中,SHBG水平与血清C反应蛋白(CRP)水平呈负相关(R = -0.489,P < 0.001)。与短等位基因重复的患者相比,具有长TAAAA重复等位基因的PCOS患者血清SHBG和游离睾酮水平显著降低,但CRP水平更高。使用TAAAA重复次数、腰臀比、胰岛素抵抗的稳态模型评估和年龄作为独立预测因子的多元线性回归模型解释了血清SHBG水平变异性的44.8%。在该模型中,发现TAAAA重复多态性是血清SHBG水平的唯一可靠预测因子(P < 0.001)。总之,TAAAA重复多态性虽影响PCOS女性的血清SHBG水平,但并非PCOS状态的主要决定因素。血清SHBG和CRP水平之间存在强烈的独立关联。CRP是心血管疾病的既定危险因素和低度炎症的标志物,是动脉粥样硬化形成的典型特征。这可能是低SHBG水平影响心血管风险的途径之一。