Association between thymine–adenine repeat polymorphisms of the estrogen receptor gene and metabolic bone disease in premature and low birth weight infants

Abstract

Abstract Background Metabolic bone disease (MBD) of prematurity is characterized by impaired skeletal mineralization accompanied by biochemical and radiological evidence of bone demineralization. The estrogen receptor (ER) plays a fundamental role in bone metabolism and has been implicated in the pathogenesis of osteoporosis, suggesting a potential influence on bone mineral density (BMD). Several polymorphic regions have been identified within the ER gene, including thymine–adenine (TA) dinucleotide repeats, where shorter repeat lengths have been linked to an increased susceptibility to fractures. Aim evaluate the association between TA repeat polymorphisms of the ER gene and the occurrence of MBD among premature low birth weight infants. Methods A case–control study was performed including 25 premature low birth weight infants diagnosed with MBD and 25 gestational age–matched premature low birth weight infants without evidence of MBD. All participants underwent detailed clinical assessment, laboratory evaluation, and molecular analysis. Genomic DNA was extracted and polymerase chain reaction (PCR) was used to determine TA repeat polymorphisms within the ER gene. Results The frequencies of homozygous low-repeat genotypes (Ho-L, < 19 repeats) and heterozygous low/high-repeat genotypes (He-LH) were significantly higher in infants with MBD, whereas the homozygous high-repeat genotype (Ho-H, > 18 repeats) predominated in controls. The Ho-L genotype was more prevalent among male infants and was associated with lower gestational age, reduced birth weight, and shorter length. Infants carrying the Ho-L genotype also demonstrated a higher requirement for mechanical ventilation. Conclusion The homozygous low TA repeat genotype of the ER gene is likely associated with an increased risk of metabolic bone disease in premature low birth weight infants. ER TA repeat polymorphisms may represent a useful genetic marker for identifying neonates at higher risk for developing MBD.