J Clin Res Pediatr Endocrinol. Ahead of Print: JCRPE-82612 | DOI: 10.4274/jcrpe.galenos.2024.2023-11-7

Estrogen Receptor 1 Gene Polymorphism and its Association with Idiopathic Short Stature in North Indian Population

Ravi Shankar Patel¹, Roshan Daniel¹, Chitra Bhardwaj¹, Anu Kumari¹, Pratibha Bawa¹, Ankita Tyagi¹, Devi Dayal², Anupriya Kaur¹, Inusha Panigrahi¹, Harvinder Kaur³, Priyanka Srivastava^1
1Genetic Metabolic Unit
²Pediatric Endocrinology Unit
³Child Growth & Anthropology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh-160012

INTRODUCTION: In the hypothalamic-pituitary-gonadotrophin (HPG) axis, estrogen plays a key role in the bone maturation regulation and growth plates closure. This study was designed to explore the link between single nucleotide polymorphisms (SNPs) in estrogen receptor 1 (ESR1) gene with idiopathic short stature (ISS) susceptibility in the North Indian population.
METHODS: Four SNPs of the ESR1 gene (rs543650, rs6557177, rs2234693 and rs9340799) were genotyped by Sanger sequencing in 52 ISS patients and 68 controls. Linkage disequilibrium (LD) and haplotyping were done by SNPstat and SHESISplus softwares. Extent of LD was determined by calculating D′ and r2 values in SNPs paired combinations.
RESULTS: A significant positive association was found between rs6557177 and rs543650 genotype and ISS susceptibility as compared to controls. The frequencies of the rs6557177 CC genotype (p=0.030; OR=0.13; 95% CI: 0.01-1.10) and rs543650 genotype TT (p =0.043; OR=0.29; 95% CI: 0.09-0.92) were observed to be increased in ISS group as compared with the control group. However, no significant correlation was observed between clinical parameters of patients and these SNPs. rs543650 shown strong LD with rs2234693 and rs9340799, similarly rs2234693 and rs9340799.
DISCUSSION AND CONCLUSION: Our study showed that CC genotype at rs6557177 and TT genotype of rs543650 of ESR1 constitutes risk factor for developing ISS in North Indian children. In the future, these findings may lead to a better understanding of the SNPs associated with ISS susceptibility.

Keywords: Genotype, Estrogen Receptor 1 gene, Haplotype, Idiopathic short stature, Linkage Disequilibrium, Single nucleotide polymorphism

---