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