上海交通大学学报（医学版）

›› 2011, Vol. 31 ›› Issue (7): 932-.doi: 10.3969/j.issn.1674-8115.2011.07.014

• 论著（临床研究） • 上一篇    下一篇

生长激素受体基因多态性与特发性矮小遗传易感性的关系

于 意1, 王 伟1, 王 莹2, 黄 嶶2, 董治亚1, 滕月春1, 倪继红1, 肖 园1, 王德芬1   

  1. 1.上海交通大学 医学院附属瑞金医院儿内科, 上海 200025； 2.国家人类基因组南方研究中心, 上海 201203
  • 出版日期:2011-07-28 发布日期:2011-07-27
  • 通讯作者: 王 伟, 电子信箱: rjwangwei@yahoo.cn。
  • 作者简介:于 意（1981—）, 女, 硕士生；电子信箱: ruyilx@gmail.com。
  • 基金资助:

    国家自然科学基金（30771029）

Associations of single nucleotide polymorphisms of growth hormone receptor with susceptibility to idiopathic short stature

YU Yi1, WANG Wei1, WANG Ying2, HUANG Wei2, DONG Zhi-ya1, TENG Yue-chun1, NI Ji-hong1, XIAO Yuan1, WANG De-fen1   

  1. 1.Department of Pediatrics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China；2.National Human Genome Center at Shanghai, Shanghai 201203, China
  • Online:2011-07-28 Published:2011-07-27
  • Supported by:

    National Natural Science Foundation of China, 30771029

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摘要：

目的 探讨人生长激素受体（GHR）基因的单核苷酸多态性（SNP）与中国汉族人群特发性矮小（ISS）遗传易感性的关系。方法 采用病例对照法，在199例ISS患儿（ISS组）和469名身高正常成人（对照组）中，对GHR基因16个SNP位点进行基因分型和比较，筛查阳性SNP位点（特异基因型频率差异有统计学意义），分析阳性SNP位点基因型与ISS发病风险及血清胰岛素样生长因子1（IGF-1）等相关临床变量的关系。结果 在ISS组和对照组中，发现3个阳性SNP位点rs6182（P=0.027）、rs4410646（P=0.01）和rs10044169（P=0.024）。①rs6182（G /T）：在T显性模式下，TT和GT基因型的ISS发病风险降低（OR=0.624，95%CI：0.402～0.969，P=0.021)。②rs4410646 （A/C）：在C显性模式下AA基因型的ISS发病风险降低（OR=0.674，95%CI：0.475～0.958，P=0.016)；该位点的多因素Logistics回归分析显示，以CC基因型为参照，血清IGF-1与基因型AA（OR=1.011，95%CI：1.002～1.020，P=0.018）和CA（OR=1.010，95%CI：1.001～1.019，P=0.037）相关；以AA基因型为参照，血清IGF-1与基因型CC相关（OR=0.989，95%CI：0.980～0.998，P=0.018）。③rs10044169（A/C）：在C显性模式下，CC和CA基因型的ISS发病风险降低（OR=0.649，95%CI：0.424～0.993，P=0.027)。结论 GHR在生长激素介导的促生长效应中起重要作用，人类GHR基因的3个SNP位点可能与ISS的遗传易感性有关。

关键词: 特发性矮小, 生长激素受体, 单核苷酸多态性, 胰岛素样生长因子1, 遗传易感性

Abstract:

Objective To investigate the associations of single nucleotide polymorphisms (SNP) of human growth hormone receptor (GHR) with genetic susceptibility to idiopathic short stature (ISS) in Chinese Han populations. Methods Case-control method was employed, and 199 children with ISS (ISS group) and 469 adults with normal weight (control group) were enrolled. Genotyping and comparison were performed in 16 SNP sites of GHR gene, positive SNP sites (significant differences in specific genotypic frequency) were screened, and the associations of genotypes of positive SNP sites with risks of ISS and related clinical variables such as serum insulinlike growth factor 1 （IGF-1）were analysed. Results Three positive SNP sites of rs6182 （P=0.027）, rs4410646 （P=0.01） and rs10044169 （P=0.024）were found in ISS group and control group. For rs6182 （G/T）, the risk of ISS of genotype TT and genotype GT decreased under T dominant mode （OR=0.624，95%CI：0.402-0.969，P=0.021). For rs4410646 (A/C), the risk of ISS of genotype AA decreased under C dominant mode （OR=0.674，95%CI：0.475-0.958，P=0.016). Multivariate Logistics regression analysis of this site revealed that serum IGF-1 was related to genotype AA （OR=1.011，95%CI：1.002-1.020，P=0.018） and genotype CA (OR=1.010，95%CI：1.001-1.019，P=0.037） with genotype CC as reference, and serum IGF-1 was related to genotype CC （OR=0.989，95%CI：0.980-0.998， P=0.018） with genotype AA as reference. For rs10044169 （A/C）, the risk of ISS of genotype CC and genotype CA significantly decreased （OR=0.649，95%CI：0.424-0.993，P=0.027) under C dominant mode. Conclusion GHR plays a role in the growth promotion effect mediated by growth hormone, and 3 SNP sites of human GHR gene may be related to genetic susceptibility to ISS.

Key words: idiopathic short stature, growth hormone receptor, single nucleotide polymorphism, insulin-like growth factor 1, susceptibility