Gao Ming, Zhu Bin, Li Ping, Zhang Guojun, Chen Kelin, Lv Hong, Ma Ruimin, Zhang Limin, Fan Yubo, Kang Xixiong
Laboratory Diagnosis Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Beijing Engineering Research Center of Immunological Reagents and Clinical Research, Beijing, China.
Front Endocrinol (Lausanne). 2018 Dec 11;9:751. doi: 10.3389/fendo.2018.00751. eCollection 2018.
Excess growth hormone (GH) secretion in acromegaly patients results in increased levels of IGF-1 expression, which causes the clinical manifestations of acromegaly. IGF-1 levels are attenuated by IGFBP3, and a polymorphism in the promoter of IGFBP3 is known to affect the circulating level of IGFBP3 protein. The aim of the study was to evaluate the association of the gene polymorphism with clinical features and surgery outcomes in acromegaly. We also investigate the difference in polymorphism between acromegaly and general population. The study included 102 acromegalic patients and 142 sex- and age-matched healthy controls. The genotyping of was carried out using the MassARRAY method. Patients were followed up for 4-12 months to estimate the neurosurgical effects. Clinical data were obtained from the medical records. The CC genotype, which is associated with decreased IGFBP3 levels, was less common in acromegaly patients than among the healthy controls; although, this correlation was not significant ( = 0.056). There was no association of the gene polymorphism with glucose, lipid, phosphorus, blood urea nitrogen, creatinine or uric acid levels. Additionally, there was no association between tumor size, texture, or hemorrhage/cyst, except there was a trend that more patients with the C allele ( = 0.054) needed additional treatment post-operation than did patients carrying the A allele (OR 1.985, 95% CI 0.983-4.008). Moreover, higher IGF-1 values after treatment were observed in patients carrying the C allele ( = 0.012 and = 0.014 according to the additive model and dominant model, respectively). Polymorphisms in may not influence metabolic parameters or pituitary tumor characteristics in acromegalic patients, but they may be associated with the hormone levels and surgery effects.
肢端肥大症患者生长激素(GH)分泌过多导致胰岛素样生长因子-1(IGF-1)表达水平升高,从而引起肢端肥大症的临床表现。IGFBP3可降低IGF-1水平,已知IGFBP3启动子中的一个多态性会影响IGFBP3蛋白的循环水平。本研究的目的是评估该基因多态性与肢端肥大症临床特征及手术结果之间的关联。我们还研究了肢端肥大症患者与普通人群在该多态性上的差异。该研究纳入了102例肢端肥大症患者和142例年龄及性别匹配的健康对照。采用MassARRAY方法对该基因进行基因分型。对患者进行了4至12个月的随访以评估神经外科手术效果。临床数据从病历中获取。与IGFBP3水平降低相关的CC基因型在肢端肥大症患者中比在健康对照中更少见;不过,这种相关性并不显著(P = 0.056)。该基因多态性与血糖、血脂、磷、血尿素氮、肌酐或尿酸水平无关。此外,肿瘤大小、质地或出血/囊肿之间无关联,不过存在一种趋势,即携带C等位基因的患者术后需要额外治疗的比例(P = 0.054)高于携带A等位基因的患者(比值比1.985,95%置信区间0.983 - 4.008)。此外,携带C等位基因的患者治疗后IGF-1值更高(根据相加模型和显性模型,P分别为0.012和0.014)。该基因的多态性可能不会影响肢端肥大症患者的代谢参数或垂体肿瘤特征,但可能与激素水平及手术效果相关。