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目的综述筛选可能影响基因重组人生长激素(recombinant human growth hormone,rhGH)促线性生长效应的候选基因及其多态性位点,为rhGH的遗传药理学研究提供依据。方法从rhGH的药理作用机制信号通路着手,选择其中重要的生物大分子,通过检索NCBI、Hapmap等网站提供的SNP位点,同时结合PubMed中相关文献报道,筛选与rhGH促线性生长效应相关的候选基因及其多态性位点。结果 rhGH的药理作用机制信号通路中2个主要的生物大分子,即生长激素受体(growth hormone re-ceptor,GHR)和胰岛素样生长因子结合蛋白-3(insulin-like growth factor binding protein-3,IGFBP-3),这2个生物大分子的编码基因上均有多个多态性位点,根据现有资料推测GHR外显子3上的fl/d3及IGFBP-3上的rs2854744(A/C)、rs3110697(G/A)、rs2132570(A/C)和rs2854746(C/G)等2个候选基因上的5个多态性位点可能与rhGH促线性生长效应有关。结论本研究拟选择GHR和IGFBP-3作为rhGH遗传药理学研究的候选基因,考察以上5个多态性位点与rhGH促线性生长效应的相关性。
OBJECTIVE: To screen candidate genes and their polymorphisms that may affect the growth-promoting effect of recombinant human growth hormone (rhGH), and provide evidence for the genetic pharmacology of rhGH. Methods Starting from the signal pathways of pharmacological mechanism of rhGH, one of the important biological macromolecules was selected. By searching SNP sites provided by NCBI, Hapmap and other websites, we also screened the candidate genes related to rhGH promoting linear growth effect Gene and its polymorphic loci. RESULTS: Two major biological macromolecules in the pharmacological mechanism of rhGH, namely, growth hormone re-ceptor (GHR) and insulin-like growth factor binding protein-3 , IGFBP-3). There are multiple polymorphic loci in the coding genes of these two biological macromolecules. Based on available data, it is speculated that fl / d3 on exon 3 of GHR and rs2854744 on IGFBP-3 (A / C), rs3110697 (G / A), rs2132570 (A / C) and rs2854746 (C / G) could be related to the growth promoting effect of rhGH. Conclusions This study was designed to select GHR and IGFBP-3 as candidate genes for genetic pharmacology study of rhGH. The correlation between these 5 polymorphic loci and the linear growth-promoting effect of rhGH was investigated.