Mercado Moisés, González Baldomero, Sandoval Carolina, Esquenazi Yoshua, Mier Fernando, Vargas Guadalupe, de los Monteros Ana Laura Espinosa, Sosa Ernesto
Endocrine Section, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, México City, México.
J Clin Endocrinol Metab. 2008 Sep;93(9):3411-5. doi: 10.1210/jc.2008-0391. Epub 2008 Jul 8.
Lack of exon 3 of the GH receptor (d3-GHR) has been associated with increased responsiveness to GH therapy. By analogy, we hypothesized that patients with acromegaly bearing the d3-GHR genotype may have a more morbid clinical and biochemical picture.
Our objective was to determine whether the GHR genotype, by modifying tissue sensitivity to GH, influences the clinical/biochemical expression of acromegaly and its outcome after treatment.
The study was conducted at a specialized clinic at a tertiary care hospital.
DESIGN, PATIENTS, AND METHODS: We conducted a prospective genotype investigation and retrospective analysis and correlation with clinical, biochemical, and outcome data from a group of 148 patients. Samples from 175 healthy blood donors were used as controls. GHR genotyping was performed by real-time PCR.
We assessed prevalence of the three GHR genotypes (fl/fl, d3/d3, and d3/fl), associations between the genotypes, and baseline as well as post-therapeutic characteristics.
Prevalence of the fl/fl, d3/d3, and d3/fl genotypes was 45, 22, and 32%, respectively, similar to what was found in the controls. Baseline characteristics were similar in carriers of the three genotypes. A positive correlation between IGF-I and log GH concentrations was significant only in homo- or heterozygous d3 carriers. Among d3-GHR carriers, diabetes, but no other comorbidities, was more prevalent (odds ratio = 2.02; 95% confidence interval = 0.96-4.2). d3-GHR carriers had significantly higher IGF-I concentrations after treatment. Multiple regression analysis revealed that the homo- or heterozygous lack of exon 3 was the strongest predictor of persistent biochemical activity (odds ratio = 1.29; 95% confidence interval = 0.65-2.58).
The absence of exon 3 of the GHR may be associated with a more morbid acromegalic clinical and biochemical picture and a lower chance of achieving IGF-I normalization after therapy.
生长激素受体第3外显子缺失（d3-GHR）与对生长激素治疗反应性增加有关。基于此，我们推测肢端肥大症患者携带d3-GHR基因型可能具有更严重的临床和生化表现。
我们的目的是确定生长激素受体基因型是否通过改变组织对生长激素的敏感性，影响肢端肥大症的临床/生化表现及其治疗后的结局。
该研究在一家三级医疗医院的专科诊所进行。
设计、患者和方法：我们对一组148例患者进行了前瞻性基因型调查以及回顾性分析，并将其与临床、生化和结局数据进行关联。来自175名健康献血者的样本用作对照。通过实时聚合酶链反应进行生长激素受体基因分型。
我们评估了三种生长激素受体基因型（fl/fl、d3/d3和d3/fl）的患病率、基因型之间的关联以及基线和治疗后的特征。
fl/fl、d3/d3和d3/fl基因型的患病率分别为45%、22%和32%，与对照组相似。三种基因型携带者的基线特征相似。胰岛素样生长因子-I（IGF-I）与生长激素对数浓度之间的正相关仅在纯合或杂合d3携带者中显著。在d3-GHR携带者中，糖尿病更为常见，但无其他合并症（优势比=2.02；95%置信区间=0.96-4.2）。d3-GHR携带者治疗后IGF-I浓度显著更高。多元回归分析显示，第3外显子的纯合或杂合缺失是持续性生化活性的最强预测因素（优势比=1.29；95%置信区间=0.65-2.58）。
生长激素受体第3外显子缺失可能与肢端肥大症更严重的临床和生化表现以及治疗后实现IGF-I正常化的可能性较低有关。
