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

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

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...

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.