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Research Article: Polymorphism analysis of estrogen receptor ? Gene RsaI and AluI in girls with idiopathic central precocious puberty: investigating the relationship and implications for early risk prediction

Date Published: 2026-06-17

Abstract:
To investigate the association between estrogen receptor ? ( ER? ) gene RsaI (rs1256049) and AluI (rs4986938) polymorphisms and the risk of idiopathic central precocious puberty (ICPP) in girls, and to provide potential molecular genetic references for early risk prediction and individualized management of ICPP. A total of 100 girls with ICPP from the Pediatric Endocrinology Clinic and Inpatient Ward of Shenzhen Maternity & Child Healthcare Hospital were enrolled, and 100 agematched healthy girls undergoing routine physical examinations during the same period served as controls. The RsaI and AluI polymorphisms of the ER? gene were genotyped using polymerase chain reactionrestriction fragment length polymorphism (PCRRFLP). Genotype and allele frequencies were compared between the two groups, and haplotype analysis was performed to evaluate combined effects of the two loci. 1.For the ER? RsaI polymorphism, significant differences were observed between the ICPP and control groups in both genotype distribution ( ? 2 = 5.96, P = 0.04) and R allele frequency (41.50% vs. 30.00%; ? 2 = 4.77, P = 0.03). The R allele was associated with an increased risk of ICPP (odds ratio [OR] = 1.58, 95% confidence interval [CI]: 1.05–2.38, P < 0.05). 2.For the AluI polymorphism, no significant differences were found in either genotype distribution or A allele frequency between the two groups ( P > 0.05). 3.Haplotype analysis of the combined RsaI and AluI polymorphisms showed a significant difference in overall haplotype distribution between the two groups (Fisher’s exact test, P = 0.02). The Rraa haplotype was more frequent in the ICPP group (39%) than in controls (31%). The ER? gene RsaI polymorphism is significantly associated with the risk of ICPP in girls. The R allele may be a susceptibility factor, and carriers of the Rr genotype appear to have a higher risk of developing ICPP. The Rraa haplotype may represent a potential risk factor for ICPP. In contrast, the AluI polymorphism shows no significant association with ICPP. These findings suggest that ER? RsaI genotyping and haplotype analysis could contribute to early risk assessment, although further multicenter studies with larger sample sizes are warranted to validate the results.

Introduction:
Idiopathic central precocious puberty (ICPP) is a developmental disorder characterized by the premature appearance of secondary sexual characteristics. The etiology of ICPP in girls remains unclear and is likely attributed to genetic polymorphisms.And there are variations in genetic background ( 1 , 2 ). The estrogen receptor (ER) plays a crucial role in the development of secondary sexual characteristics and the pubertal growth spurt in females ( 3 – 6 ). Studies have indicated that ER? gene polymorphisms may…

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