| Thyroid peroxidase gene variants and susceptibility to congenital hypothyroidism and autoimmune thyroid disease among Egyptian pediatric cohort |
Hala M. Sakhr1 
, Mohammed H. Hassan2,3
, Esraa Abbass Abdallah4, Amira Mahmoud Ewis1, Mohamed Hesham Mohamed1, Shymaa Gaber Rizk1 |
1Department of Pediatrics, Faculty of Medicine, Qena University, Qena, Egypt
2Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Qena University, Qena, Egypt
3Department of Pathology, College of Medicine, Qassim University, Buraydah, Kingdom of Saudi Arabia
4Department of Clinical Pathology, Faculty of Medicine, Qena University, Qena, Egypt |
Correspondence:
Hala M. Sakhr, Email: hala.sakhr@med.svu.edu.eg
Mohammed H. Hassan, Email: mohammedhosnyhassaan@yahoo.com
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Received: 20 December 2025 • Revised: 21 January 2026 • Accepted: 3 February 2026 |
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| Abstract |
Background
Pediatric thyroid disorders arise from complex interactions among genetic susceptibility, immune dysregulation, and metabolic factors that influence their onset and severity.
Purpose
This study aimed to evaluate the clinical, biochemical, micronutrient, and genetic determinants of thyroid dysfunction in children with particular emphasis on the thyroid peroxidase (TPO) Arg386His and Thr725Pro polymorphisms.
Methods
This case-control study enrolled 150 Egyptian children aged 2–15 years, including 50 with congenital hypothyroidism (CH), 50 with autoimmune thyroiditis (AIT), and 50 controls. The participants underwent clinical assessments, routine laboratory investigations, thyroid function tests, and tests for selenium, copper, and thyroid autoantibodies (Tg Abs and TPO Abs). Following genomic DNA extraction from peripheral blood, the TPO gene polymorphisms (Arg386His and Thr725Pro) were analyzed using polymerase chain reaction-restriction fragment length polymorphism.
Results
Children with thyroid disorders exhibit a higher prevalence of anemia and significantly lower ferritin levels. Profound micronutrient disturbances were evident and characterized by severe selenium deficiency and elevated copper concentrations. The genetic analysis demonstrated a strong association between the TPO exon-8 Arg386His polymorphism and pediatric thyroid disorders. The His allele and His-containing genotypes were significantly more frequent among cases, particularly in children with CH. A genotype-phenotype correlation revealed that the histidine/histidine (His/His) genotype was consistently associated with the highest serumthyroid-stimulating hormone levels in both CH and
AIT, suggesting greater functional impairment of thyroid hormone synthesis. Distinct genetic patterns were observed between disease subtypes, with a predominance of the His allele in CH and the Arg allele in AIT. No variation was detected in the Thr725Pro polymorphism, and all participants exhibited the Thr/Thr genotype.
Conclusion
These findings support a multifactorial model of pediatric thyroid disease, with the TPO Arg386His variant, particularly the His/His genotype, emerging as a key genetic contributor to disease susceptibility and severity. |
| Key Words:
Autoimmune thyroiditis, Congenital hypothyroidism, TPO gene polymorphisms |
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