PDF(Pubmed)
Abstract：
OBJECTIVE: Components of the hypothalamic-pituitary axis (HPA) pathway are potential mediators of the genetic risk of polycystic ovarian syndrome (PCOS). Impaired glucocorticoid receptor (NR3C1) expression and function may underlie impaired HPA-axis cortisol activity, thereby also contributing to the increased adrenal cortisol and androgen production present in women with PCOS. In this study, we aimed to identify whether NR3C1 is linked or in linkage disequilibrium (LD), that is, linkage joint to association, with PCOS in Italian peninsular families.
METHODS: In 212 Italian families with type 2 diabetes (T2D) from the Italian peninsula, previously recruited for a T2D study and phenotyped for PCOS, we used microarray to genotype 25 variants in the NR3C1 gene. We analyzed the 25 NR3C1 variants by Pseudomarker parametric linkage and LD analysis.
RESULTS: We found the novel implication in PCOS risk of two intronic variants located within the NR3C1 gene (rs10482672 and rs11749561), thereby extending the phenotypic implication related to impaired glucocorticoid receptor.
CONCLUSIONS: To the best of our knowledge, this is the first study to report NR3C1 as a risk gene in PCOS.
METHODS: In 212 Italian families with type 2 diabetes (T2D) from the Italian peninsula, previously recruited for a T2D study and phenotyped for PCOS, we used microarray to genotype 25 variants in the NR3C1 gene. We analyzed the 25 NR3C1 variants by Pseudomarker parametric linkage and LD analysis.
RESULTS: We found the novel implication in PCOS risk of two intronic variants located within the NR3C1 gene (rs10482672 and rs11749561), thereby extending the phenotypic implication related to impaired glucocorticoid receptor.
CONCLUSIONS: To the best of our knowledge, this is the first study to report NR3C1 as a risk gene in PCOS.
摘要：
目的：下丘脑-垂体轴（HPA）通路的组成部分是多囊卵巢综合征（PCOS）遗传风险的潜在介质。糖皮质激素受体（NR3C1）表达和功能受损可能是HPA轴皮质醇活性受损的基础，因此也有助于PCOS女性中肾上腺皮质醇和雄激素产生的增加。在这项研究中,我们的目的是确定NR3C1是否连接或连锁不平衡(LD)，也就是说,连接接头到协会，意大利半岛家庭的PCOS。
方法：在来自意大利半岛的212个患有2型糖尿病（T2D）的意大利家庭中，以前招募的T2D研究和PCOS表型，我们使用微阵列对NR3C1基因中的25个变异进行了基因分型.我们通过Pseudomarker参数连锁和LD分析分析了25个NR3C1变体。
结果：我们发现了位于NR3C1基因内的两个内含子变体（rs10482672和rs11749561）在PCOS风险中的新含义，从而扩展了与糖皮质激素受体受损相关的表型含义。
结论：据我们所知，这是首次报道NR3C1作为PCOS风险基因的研究。
方法：在来自意大利半岛的212个患有2型糖尿病（T2D）的意大利家庭中，以前招募的T2D研究和PCOS表型，我们使用微阵列对NR3C1基因中的25个变异进行了基因分型.我们通过Pseudomarker参数连锁和LD分析分析了25个NR3C1变体。
结果：我们发现了位于NR3C1基因内的两个内含子变体（rs10482672和rs11749561）在PCOS风险中的新含义，从而扩展了与糖皮质激素受体受损相关的表型含义。
结论：据我们所知，这是首次报道NR3C1作为PCOS风险基因的研究。
