Carrascosa A, Audí L, Fernández-Cancio M, Esteban C, Andaluz P, Vilaró E, Clemente M, Yeste D, Albisu M A, Gussinyé M
Department of Pediatrics, Institut de Recerca, Hospital Vall d'Hebron, Centre for Biomedical Research on Rare Diseases, Autonomous University, Barcelona, Spain.
J Clin Endocrinol Metab. 2008 Mar;93(3):764-70. doi: 10.1210/jc.2007-2180. Epub 2007 Dec 26.
Consensus is lacking as to whether the exon 3-deleted (d3)/full-length (fl) GH receptor (GHR) polymorphism is associated with responsiveness to GH therapy.
Our objective was to evaluate, in short, prepubertal, appropriate-for-gestational age (AGA) patients, 2-yr growth response to GH therapy (31.7+/-3.5 microg/kg.d) according to exon 3-deleted/full-length GHR genotypes.
We conducted a retrospective study.
We studied 106 short AGA children, 58 boys and 48 girls, 7.8+/-2.3 yr, (d3/d3 n=18, d3/fl n=42, and fl/fl n=46). The GH response to two provocative stimuli were under 10 ng/ml in 65 and one or both over 10 ng/ml in 41 patients.
Patients were followed by a single clinical team and remained prepubertal during the study. The exon 3-deleted/full-length GHR genotypes were determined and analyzed in the same hospital.
Growth velocity significantly (P<0.0001) increased during the first and second years of therapy, as did height sd score (SDS). These increases were similar in each exon 3-deleted/full-length GHR genotype. Total 2-yr height gain (SDS) did not differ statistically among genotypes: 15.5+/-2.2 cm and 1.2+/-0.5 SDS in d3/d3, 15.9+/-2.0 cm and 1.3+/-0.4 SDS in d3/fl, and 15.4+/-2.1 cm and 1.1+/-0.3 SDS in fl/fl. No significant differences among the three genotypes were found in both sexes or in patients with different GH peak response to provocative stimuli for these parameters. An analysis of previously published studies was also performed.
These results confirm in AGA patients those previously found by us and others in small-for-gestational-age patients and suggest that neither sex nor GH peaks after provocative stimuli might influence significantly the responsiveness to GH therapy according to the exon 3-deleted/full-length GHR genotypes.
关于外显子3缺失（d3）/全长（fl）生长激素受体（GHR）多态性是否与生长激素治疗反应性相关，目前尚无共识。
我们的目的是评估2至青春期前、适于胎龄（AGA）的矮小患者，根据外显子3缺失/全长GHR基因型，对生长激素治疗（31.7±3.5微克/千克·天）的2年生长反应。
我们进行了一项回顾性研究。
我们研究了106名矮小AGA儿童，58名男孩和48名女孩，年龄7.8±2.3岁，（d3/d3基因型18例，d3/fl基因型42例，fl/fl基因型46例）。65例患者对两种激发刺激的生长激素反应低于10纳克/毫升，41例患者一种或两种反应高于10纳克/毫升。
患者由单一临床团队随访，研究期间仍处于青春期前。外显子3缺失/全长GHR基因型在同一家医院测定和分析。
治疗的第一年和第二年生长速度显著增加（P<0.0001），身高标准差评分（SDS）也增加。这些增加在每种外显子3缺失/全长GHR基因型中相似。各基因型之间2年总身高增加（SDS）无统计学差异：d3/d3基因型为15.5±2.2厘米和1.2±0.5 SDS，d3/fl基因型为15.9±2.0厘米和1.3±0.4 SDS，fl/fl基因型为15.4±2.1厘米和1.1±0.3 SDS。在这些参数方面，三种基因型在性别或对激发刺激生长激素峰值反应不同的患者中均未发现显著差异。我们还对先前发表的研究进行了分析。
这些结果在AGA患者中证实了我们和其他人先前在小于胎龄患者中发现的结果，并表明根据外显子3缺失/全长GHR基因型，性别和激发刺激后的生长激素峰值均不会显著影响对生长激素治疗的反应性。
