Kaya Z, Caglayan S, Akkiprik M, Aral C, Ozisik G, Ozata M, Ozer A
Department of Medical Biology, School of Medicine, Marmara University, Başıbüyük Mah., Maltepe Başıbüyük Yolu Sok., No: 9/1, Maltepe, 34854, Istanbul, Turkey.
Department of Medical Biology, School of Medicine, Yuzuncu Yıl University, Van, Turkey.
J Endocrinol Invest. 2016 May;39(5):557-66. doi: 10.1007/s40618-015-0409-1. Epub 2015 Nov 23.
The metabolic syndrome (MetS) is characterized by a cluster of metabolic factors, including insulin resistance and type-2 diabetes, abdominal obesity, dyslipidemia, hypertension and microalbuminuria. Impaired glucocorticoid receptor (GR) activity also plays an important role in the etiology of MetS. The objective of our study is to evaluate the effects of GR gene polymorphisms (BclI, N363S, TthIII1 and ER22/23EK) in Turkish patients with MetS.
Seventy subjects with MetS and 185 healthy controls were enrolled in the study. PCR-RFLP analysis was used for genotyping. Results for each polymorphism have been verified by allele-specific oligonucleotide analysis.
BclI GG genotype was significantly associated with an increased risk of MetS (p = 0.02). Also, only in women, the G allele carriers were significantly associated with higher C-peptide. T allele carriers of TthIII1 polymorphism were significantly associated with higher C-peptide, triglyceride, insulin and C-reactive protein (CRP, p value 0.048, 0.022, 0.005 and 0.022, respectively), and lower fasting blood glucose (FBG, p = 0.02). The combined carriers of BclI polymorphism G allele and TthIII1 polymorphism T allele were significantly associated with higher diastolic blood pressure in all patients, and lower FBG and postprandial blood glucose in only men. All the ER22/23EK polymorphisms coexisted with polymorphic variant of TthIII1 (p = 0.0058).
The presence of homozygote polymorphic variant of BclI might be good predictive markers for the disease susceptibility. The BclI and the TthIII1 polymorphism are associated with sex-specific clinical parameters. Our findings also suggest that the combination of BclI and TthIII1 polymorphisms may play a protective role in blood glucose.
代谢综合征（MetS）的特征是一系列代谢因素，包括胰岛素抵抗和2型糖尿病、腹部肥胖、血脂异常、高血压和微量白蛋白尿。糖皮质激素受体（GR）活性受损在MetS的病因中也起重要作用。我们研究的目的是评估GR基因多态性（BclI、N363S、TthIII1和ER22/23EK）在土耳其MetS患者中的影响。
本研究纳入了70例MetS患者和185例健康对照。采用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）进行基因分型。每个多态性的结果均通过等位基因特异性寡核苷酸分析进行了验证。
BclI GG基因型与MetS风险增加显著相关（p = 0.02）。此外，仅在女性中，G等位基因携带者与较高的C肽显著相关。TthIII1多态性的T等位基因携带者与较高的C肽、甘油三酯、胰岛素和C反应蛋白（CRP，p值分别为0.048、0.022、0.005和0.022）以及较低的空腹血糖（FBG，p = 0.02）显著相关。BclI多态性G等位基因和TthIII1多态性T等位基因的联合携带者在所有患者中与较高的舒张压显著相关，而仅在男性中与较低的FBG和餐后血糖相关。所有ER22/23EK多态性均与TthIII1的多态性变体共存（p = 0.0058）。
BclI纯合子多态性变体的存在可能是疾病易感性的良好预测标志物。BclI和TthIII1多态性与性别特异性临床参数相关。我们的研究结果还表明，BclI和TthIII1多态性的组合可能在血糖方面起保护作用。
