Costalonga Everlayny Fiorot, Antonini Sonir R, Guerra-Junior Gil, Mendonca Berenice Bilharinho, Arnhold Ivo J P, Jorge Alexander A L
Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM/42, Faculdade de Medicina da Universidade de Sao Paulo, São Paulo, Brazil.
J Clin Endocrinol Metab. 2009 Feb;94(2):588-95. doi: 10.1210/jc.2008-1608. Epub 2008 Nov 4.
Genetic factors that influence the response to recombinant human GH (rhGH) therapy remain mostly unknown. To date, only the GH receptor gene has been investigated.
The aim of the study was to assess the influence of a polymorphism in the IGF-binding protein-3 (IGFBP-3) promoter region (-202 A/C) on circulating IGFBP-3 levels and growth response to rhGH therapy in children with GH deficiency (GHD).
-202 A/C IGFBP3 genotyping (rs2854744) was correlated with data of 71 children with severe GHD who remained prepubertal during the first year of rhGH treatment.
We measured IGFBP-3 levels and first year growth velocity (GV) during rhGH treatment.
Clinical and laboratory data at the start of treatment were indistinguishable among patients with different -202 A/C IGFBP3 genotypes. Despite similar rhGH doses, patients homozygous for the A allele presented higher IGFBP-3 sd score levels and higher mean GV in the first year of rhGH treatment than patients with AC or CC genotypes (first year GV, AA = 13.0 +/- 2.1 cm/yr, AC = 11.4 +/- 2.5 cm/yr, and CC = 10.8 +/- 1.9 cm/yr; P = 0.016). Multiple linear regression analyses demonstrated that the influence of -202 A/C IGFBP3 genotype on IGFBP-3 levels and GV during the first year of rhGH treatment was independent of other variables.
The -202 A allele of IGFBP3 promoter region is associated with increased IGFBP-3 levels and GV during rhGH treatment in prepubertal GHD children.
影响重组人生长激素（rhGH）治疗反应的遗传因素大多仍不明确。迄今为止，仅对生长激素受体基因进行了研究。
本研究旨在评估胰岛素样生长因子结合蛋白3（IGFBP-3）启动子区域（-202 A/C）多态性对生长激素缺乏症（GHD）患儿循环IGFBP-3水平及rhGH治疗生长反应的影响。
对71例重度GHD患儿进行-202 A/C IGFBP3基因分型（rs2854744），这些患儿在rhGH治疗的第一年仍处于青春期前。
我们测量了rhGH治疗期间的IGFBP-3水平和第一年生长速度（GV）。
不同-202 A/C IGFBP3基因型患者治疗开始时的临床和实验室数据相似。尽管rhGH剂量相似，但与AC或CC基因型患者相比，A等位基因纯合子患者在rhGH治疗的第一年IGFBP-3标准差评分水平更高，平均GV更高（第一年GV，AA = 13.0±2.1厘米/年，AC = 11.4±2.5厘米/年，CC = 10.8±1.9厘米/年；P = 0.016）。多元线性回归分析表明，-202 A/C IGFBP3基因型对rhGH治疗第一年IGFBP-3水平和GV的影响独立于其他变量。
IGFBP3启动子区域的-202 A等位基因与青春期前GHD患儿rhGH治疗期间IGFBP-3水平升高和GV增加有关。
