Study of Estrogen Receptor Gene Thymine-Adenine Repeat Polymorphisms in Low Birth Weight and Premature Infants with Bone Disease
Authors: Khalaf Randa I , Kamal Tarek M , Dawoud Mohamed O , Shawky Rabah M , Hamed Heba A Abdel , Gaber Elham M 
Published: November 2024

Introduction

Metabolic Bone disease (MBD) of prematurity is a disorder of bone health with hypocalcemia, hypo or hyperphosphatemia and radiological findings of bone demineralization. MBD often presents in newborns &lt;28wks of gestation in 16-40% of VLBW and ELBW (Rustico et al., 2014). Several pathophysiological conditions have been suggested as factors behind MBD including inadequate supply of calcium and phosphorus. as well as side effects of some drugs as corticosteroids (Lothe et al., 2011 & Sharma and Sohi, 2012). Genetic predisposition to low bone mass content (BMC) in premature infants have been studied lately (Saraff et al., 2021). Estrogen Receptor (ER), a group of nuclear receptor superfamily members has been recently implicated in the development of osteoporosis suggesting the use of its gene as a possible candidate gene for bone mineral density (BMD) (Gennari et al. 2005). The targeted deletion of ER in mice has affected the periosteum (Clancy et al., 2017). Having several polymorphic sites for ER, the low number of Thymine adenine repeats (Ho-L) was found to relate with increased fracture risk or BMD in certain populations (Rooney et al., 2017).

Aim of the Work

Studying the relation between allelic polymorphism of Thymine Adenine repeats variant of ER gene and metabolic bone disease in low birth weight and premature infants.

Patients and Methods

A case-controlled study conducted at NICU Ain Shams University Hospitals starting from February 2022 till February 2023. Inclusion criteria: Cases (25): VLBW premature infants with bone disease evidenced by laboratory data (low calcium, low phosphorous and high alkaine phosphatase. (Hung et al., 2011) serving as group 1. Controls (25): VLBW premature infants without bone disease evidenced by normal laboratory data, serving as group 2. Exclusion criteria: Full term infants, or premature infants with syndromic features suggesting genetic diseases or chromosomal anomalies. Parents of patients signed an informed consent before being enrolled to this study and after approval of Ethical committee Ain Shams University. All patients and controls were subjected to the following: Full history taking and examination with special emphasis on length, weight and their SDS, gestational age. Laboratory sample for measurement of ALP, Calcium, phosphorous. Genomic DNA was extracted then amplified by PCR to study TA repeats of ER using gene jet purification mini kit (Kany et al., 2019).

Results

Group 1 had a percent of females and males of 58 and 48% respectively. their birth weight SD ranged from -6.8 to -3.86 while length SD ranged from -2.8 to -3.6. According to laboratory parameters; there was statistically significant decrease in the level of Ca (8.41 ± 0.86) and Phosphorus (1.96 ± 0.43)and increase in alkaline phosphatase (935.60 ± 50.83) among group 1 compared to group 2. Genotyping of TA repeats of ER, Ho-L(homo with low T-A repeated sequences &lt;19), He-LH(hetero with low and high T-A repeated sequences &lt;19 and&gt;18) were statistically significantly higher in Group 1, while Ho-H(homo with high T-A repeated sequences &gt;18) was significantly higher among group 2. There was a statistically significant increase of Ho-L in males more than females. Also gestational age, birth weight and birth length were less in Ho-L group. Percentage of infants on mechanical ventilation was higher among those with Ho-L group.

Conclusion

This study concluded that premature infants with less TA repeats of ER gene showed higher incidence of MBD, suggesting the possible link between TA repeats of ER gene with the development of MBD.