J Clin Res Pediatr Endocrinol. 2024; 16(3): 279-287 | DOI: 10.4274/jcrpe.galenos.2024.2023-11-7

Estrogen Receptor 1 Gene Polymorphism and its Association with Idiopathic Short Stature in a 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
1Postgraduate Institute of Medical Education and Research (PGIMER), Advanced Pediatrics Centre, Genetic and Metabolic Unit, Chandigarh, India
²Postgraduate Institute of Medical Education and Research (PGIMER), Advanced Pediatrics Centre, Pediatric Endocrinology Unit, Chandigarh, India
³Postgraduate Institute of Medical Education and Research (PGIMER), Advanced Pediatrics Centre, Child Growth and Anthropology Unit, Chandigarh, India

INTRODUCTION: In the hypothalamic-pituitary-gonadotrophin axis, estrogen plays a key role in the regulation of bone maturation and growth plate closure. This study was designed to explore the link between single nucleotide polymorphisms (SNPs) in the estrogen receptor 1 (ESR1) gene with idiopathic short stature (ISS) susceptibility in a North Indian population.
METHODS: Four SNPs of ESR1 (rs543650, rs6557177, rs2234693 and rs9340799) were genotyped by Sanger sequencing in ISS patients and controls. Linkage disequilibrium (LD) and haplotyping were done by SNPStat and SHEsisPlus software. The extent of LD was determined by calculating D’ and R2 values in SNP paired combinations.
RESULTS: Fifty-two ISS patients were compared with 68 controls. A significant positive association was found between rs6557177 and rs543650 genotype and ISS susceptibility. The frequencies of the rs6557177 CC genotype [p=0.030; odds ratio (OR)=0.13; 95% confidence interval (CI): 0.01-1.10] and rs543650 genotype TT (p=0.043; OR=0.29; 95% CI: 0.09-0.92) were increased in the ISS group compared with controls. However, no significant correlation was observed between clinical parameters of patients and these SNPs. rs543650 showed strong LD with rs2234693 and rs9340799, similarly rs2234693 and rs9340799.
DISCUSSION AND CONCLUSION: Our study showed that the CC genotype at rs6557177 and TT genotype at rs543650 of ESR1 constituted a risk factor for developing ISS in North Indian children. 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

---

CITE