Association of single nucleotide polymorphisms in estrogen receptor 1 gene with the risk of idiopathic short stature

Abstract

Estrogen is a hormone in hypothalamic-pituitary-gonadal (HPG) axis that plays an important role in the regulation of bone maturation and closure of the growth plate. The aim of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in estrogen receptor 1 (ESR1) gene and susceptibility to idiopathic short stature (ISS) in the Chinese population. Six SNPs of the ESR1 gene (rs6557177, rs1884049, rs3020429, rs3798575, rs3778090, rs3798757) were genotyped and we found a significant positive association between rs6557177 genotype and susceptibility to ISS compare to control group in preliminary study (ISS=200, control=220, χ 2 =6.262, P =0.044). Validation of rs6557177 was conducted by further expanding the sample size to 400 ISS patients and 380 control subjects genotyped by SNaPshot Multiplex System. The frequencies of the rs6557177 CC genotype and C allele were observed to increased in ISS group compared with the control group (χ 2 =9.913, P =0.007; χ 2 =5.57, P = 0.018 OR: 1.502; 95% CI: 1.07-2.108 respectively). However, no significant correlation was observed between the rs6557177 and clinical characteristics of the study participants. We demonstrate for the first time that the presence of a C allele or CC genotype at rs6557177 of ESR1 constitutes risk factor for developing ISS in Chinese children.