人糖皮质激素受体基因3个多态性与肥胖、高血压和糖尿病关系的5年随访研究

Roland Rosmond MD, PhD, Göran Holm MD, PhD
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引用次数: 37

摘要

糖皮质激素受体(GRs)是调节皮质醇表达的细胞质受体,与染色质上的特定位点结合。糖皮质激素受体基因(GRL)位于染色体5q31上,编码777氨基酸(GRα)或742氨基酸(GRβ)多肽。本研究的目的是检验GRL基因的3个多态性——启动子区的Tth111I限制性片段、内含子2的BclI多态性和外显子2的a/G多态性——与163名1944年出生的无关瑞典男性肥胖、高血压和糖尿病的估计之间的前瞻性关联。这些数据显示,在5年的随访中,罕见BclI等位基因纯合子的体重、体重指数、腹部肥胖、空腹血糖、胰岛素和稳态模型评估显著增加。相反,并没有检测到与Tth111I或A/G多态性的显著关联。结论:GRL的遗传信息将有助于肥胖、糖尿病和相关代谢疾病的进一步遗传学研究。
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A 5-Year Follow-Up Study of 3 Polymorphisms in the Human Glucocorticoid Receptor Gene in Relation to Obesity, Hypertension, and Diabetes

Glucocorticoid receptors (GRs) are cytoplasmatic receptors regulating the expression of cortisol and bind to specific sites on chromatin. The glucocorticoid receptor gene (GRL) is located on chromosome 5q31 and encodes for either a 777-amino acid (GRα) or a 742-amino acid (GRβ) polypeptide. The objective of the current study was to examine the prospective association of 3 polymorphisms—a Tth111I restriction fragment in the promoter region, a BclI polymorphism in intron 2, and an A/G polymorphism in exon 2—of the GRL gene on estimates of obesity, hypertension, and diabetes in 163 unrelated Swedish men born in 1944. These data showed a significant increase in body weight, body mass index, abdominal obesity, fasting glucose, insulin, and homeostasis model assessment over the 5-year follow-up among homozygotes for the rare BclI allele. In contrast, no significant associations with the Tth111I or A/G polymorphism were detected. It is concluded that the genetic information about GRL would be useful for further genetic study of obesity, diabetes, and related metabolic diseases.

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