مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Age-Stratified Evaluation of Common Polymorphisms in Thalassemia Among the Iranian Population: A Genomic Perspective (Research paper)
Age-Stratified Evaluation of Common Polymorphisms in Thalassemia Among the Iranian Population: A Genomic Perspective (Research paper)
Majid Mesgar Tehrani,1,*Amir Modarresi Chahardehi,2Reza Mirlohi,3Mohammad Mahdi Eslami,4
1. Member of the Core Committee of the National Genomics Hub, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2. Amir Research Institute, Tehran, Iran 3. Member of the Bioinformatics Research Group, Nasim Research Institute, Tehran, Iran 4. Member of the Bioinformatics Research Group, Nasim Research Institute, Tehran, Iran
Introduction: Thalassemia refers to a genetically heterogeneous group of inherited hemoglobinopathies caused by mutations in globin genes, resulting in impaired hemoglobin synthesis. These defects lead to imbalanced globin chain production, accumulation of unpaired insoluble chains, ineffective erythropoiesis, and hemolytic anemia. Beta-thalassemia (BT) is one of the most prevalent autosomal recessive monogenic disorders worldwide. Its most severe form, beta-thalassemia major (BTM), arises from mutations in the HBB gene on chromosome 11, resulting in the absence of beta-globin chain production. We aimed to characterize the prevalence and distribution of common thalassemia-related polymorphisms in the Iranian population across age strata and to explore pharmacogenetic signals related to adverse drug reactions (ADRs) in thalassemia care.
Methods: We curated variant-level data from NCBI resources and performed a pharmacogenetic aggregation using MegaGen software. Analyses summarized the frequency of common variants and annotated candidate genotype–ADR links reported for drugs used in thalassemia management. Variants were grouped by gene and reference SNP (RS) identifiers; exploratory age-stratified descriptive comparisons were performed across pediatric, adolescent, and adult groups.
Results: The most frequently cataloged loci were HBB (13.11%), ADIPOQ (6.01%), and HBG2 (5.46%). Within these genes, recurrent RS identifiers included HBB (RS334, RS33946267, RS33930165), ADIPOQ (RS2241766, RS17300539, RS822396), and HBG2 (RS7482144, RS34474104, RS36049074). Therapeutics commonly discussed in thalassemia care or investigation included deferasirox, mitapivat, rapamycin, and daratumumab. Notably, deferasirox (Exjade/Jadenu) has recognized hepatotoxicity signals; our pharmacogenetic screen highlighted a putative association framework for ADR susceptibility, with literature-referenced signals involving loci such as FTO (e.g., rs1421085) warranting targeted validation. Age-stratified summaries suggested differences in the distribution of variant burden across strata; detailed subgroup estimates will be presented.
Conclusion: In this Iranian cohort, HBB, ADIPOQ, and HBG2 harbor the majority of commonly referenced polymorphisms relevant to thalassemia biology and care. Coupling variant frequency data with pharmacogenetic annotation underscores the potential to anticipate ADR risk—particularly for iron chelators such as deferasirox—and to prioritize genotype-informed monitoring. Prospective, phenotype-linked studies with harmonized age strata are needed to validate genotype–ADR associations and to translate these findings into precision dosing and surveillance algorithms in Iran.