Growth hormone receptor isoforms and fracture risk in adult-onset growth hormone-deficient patients
Growth hormone receptor isoforms and fracture risk in adult-onset growth hormone-deficient patients
复制标题
DOI：
10.1111/cen.13161
复制
发表时间：
2016-11-01
影响因子：
3.2
通讯作者：
De Marinis, L.
中科院分区：
文献类型：
--
作者：
Mormando, M.;Chiloiro, S.;De Marinis, L.
前言生长激素缺乏被认为是决定骨质疏松患者骨骼脆性的最重要因素。成骨细胞和软骨细胞表达生长激素（GH）受体。已鉴定出两种GH受体亚型（GHRi）：它们的差异在于存在/不存在GHR基因外显子3编码的蛋白片段。因此，鉴定了三种基因型：两种全长蛋白质的携带者（flfl-GHR）、一种全长蛋白质和一种缺失蛋白质的携带者（fld 3-GHR）以及两种缺失蛋白质的携带者（d3 d3-GHR）。这种多态性赋予了对内源性GH和重组人GH（rhGH）更高的敏感性;其对骨代谢和骨骼脆性的影响尚不清楚。这篇文章的目的是探讨GHRi在预测骨骼脆弱性在成人发病GHD（AO-GHD）patients.Subjects和methodsA横断面研究进行了调查之间的关联d3-GHR亚型和患病率的形态椎骨骨折（VF）在AO-GHD的作用。入组了93例AO-GHD患者。49名患者携带flfl-GHRi（527%），44名患者（473%）携带d3-GHR同种型的至少一个等位基因。记录了32例VF。57例患者进行了rhGH替代therapy.ResultsMedian年龄显着较高的骨折患者相比，非骨折的d3载体患者表现出较低的VF风险相比，flfl-GHRi（OR：037，95%IC：024-055，P < 00001）。这一发现也证实了在AO-GHD进行rhGH替代therapy.ConclusionThis研究表明，D3-GHR可能会保护AO-GHD，特别是当用rhGH治疗的风险VF。
IntroductionGrowth hormone deficiency is considered the most important factor determining skeletal fragility in hypopituitary patients. Osteoblasts and chondrocytes express growth hormone (GH) receptor. Two GH receptor isoforms (GHRi) have been identified: they differ for the presence/absence of a protein fragment encoded by exon 3 of GHR gene. Consequently, three genotypes were identified: carriers of both the full-length proteins (flfl-GHR), carriers of one full-length protein and one deleted protein (fld3-GHR) and carriers of both deleted proteins (d3d3-GHR). This polymorphism confers a higher sensitivity to endogenous GH and to recombinant human GH (rhGH); its effect on bone metabolism and skeletal fragility is unknown. The aim of this article was to investigate the role of GHRi in predicting skeletal fragility in adult-onset GHD (AO-GHD) patients.Subjects and methodsA cross-sectional study was conducted to investigate the association between the d3-GHR isoform and the prevalence of morphometric vertebral fractures (VFs) in AO-GHD. Ninety-three AO-GHD were enrolled. Forty-nine patients carried flfl-GHRi (527%), and 44 patients (473%) carried at least one allele of the d3-GHR isoform. Thirty-two VFs were documented. Fifty-seven patients underwent rhGH replacement therapy.ResultsMedian age was significantly higher in fractured patients as compared to nonfractured ones; d3-carrier patients showed a lower VF risk as compared to flfl-GHRi (OR: 037, 95% IC: 024-055, P < 00001). This finding was also confirmed in AO-GHD undergoing rhGH replacement therapy.ConclusionThis study suggests that d3-GHR may protect AO-GHD particularly when treated with rhGH from the risk of VFs.