Follicle-Stimulating Hormone Receptor Polymorphism (G-29A) Is Associated with Altered Level of Receptor Expression in Granulosa Cells
Follicle-Stimulating Hormone Receptor Polymorphism (G-29A) Is Associated with Altered Level of Receptor Expression in Granulosa Cells
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DOI：
10.1210/jc.2011-1064
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发表时间：
2011-09-01
影响因子：
5.8
通讯作者：
Mahale, Smita D.
中科院分区：
文献类型：
--
作者：
Desai, Swapna S.;Achrekar, Swati K.;Mahale, Smita D.
背景：在接受体外受精（IVF）治疗的受试者中，FSHR基因的多态性与卵巢对FSH刺激的不同反应有关。卵巢反应的类型与颗粒细胞上FSH受体（FSHR）的表达水平相关。目的：探讨FSHR基因启动子-29位点多态性是否与受体表达改变有关。设计与患者：在100例接受IVF治疗的受试者中研究-29位FSHR多态性。回顾性分析该多态性与FSHR表达水平的关系。环境：本研究在学术研究所和私人试管婴儿诊所进行。方法：采用聚合酶链反应-限制性片段长度多态性方法研究体外受精患者FSHR基因-29位点基因型。从颗粒细胞中提取总RNA和蛋白。实时荧光定量PCR检测FSHR mRNA的相对表达量。Western blot和共聚焦显微镜检测受体蛋白表达。结果：临床和内分泌指标显示，FSHR基因-29位AA基因型的受试者中，近72%为卵巢不良反应（优势比8.63,95%可信区间1.84 ~ 45.79,P = 0.001）。与G等位基因相比，A等位基因的剪切强度较低，说明两者的结合亲和力存在差异。AA基因型与GG基因型相比，FSHR在mRNA和蛋白水平上的相对表达量均显著降低。结论：FSHR基因-29位AA基因型受试者卵巢反应较差是由于受体表达减少所致。[J] .中华临床内分泌杂志，2011,31(5):557 - 557。
Context: Polymorphisms of the FSHR gene are associated with variable ovarian response to FSH stimulation in subjects undergoing in vitro fertilization (IVF) treatment. The type of ovarian response is correlated with the level of FSH receptor (FSHR) expression on granulosa cells.Objective: We investigated whether the polymorphism at position -29 in the promoter of the FSHR gene may contribute in altered receptor expression.Design and patients: FSHR polymorphism at position -29 was studied in 100 subjects undergoing IVF treatment. Association of this polymorphism with level of FSHR expression was retrospectively analyzed.Setting: The study was conducted at an academic research institute and private IVF clinic.Methods: The genotype at position -29 of the FSHR gene was studied in IVF subjects by PCR-restriction fragment length polymorphism. Total RNA and protein was extracted from granulosa cells. The relative FSHR mRNA expression was carried out by real-time PCR. The receptor protein expression was evaluated by Western blot and confocal microscopy.Results: The clinical and endocrinological parameters revealed that almost 72% of subjects with the AA genotype at position -29 of FSHR gene were poor ovarian responders (odds ratio 8.63, 95% confidential interval 1.84-45.79; P = 0.001). The lower cleavage intensity predicted by in silico analysis for A allele as compared with the G allele suggest the difference in the DNA-protein binding affinity. The relative expression of FSHR at mRNA and protein level was significantly reduced in subjects with AA genotype as compared with the GG genotype.Conclusion: Poor ovarian response observed in subjects with the AA genotype at position -29 of the FSHR gene is due to reduced receptor expression. (J Clin Endocrinol Metab 96: 2805-2812, 2011)