• Common Polymorphisms Associated with Beta-Thalassemia Minor
  • Dr. Majid MesgarTehrani,1,* Fatima yarahmadi,2 Dr. Mohammad Mahdi Eslami,3 Dr. Reza Mirlohi,4
    1. Member of the Core Committee of the National Genomics Hub, Shahid Beheshti University of Medical Sciences, 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: Minor thalassemia is one of the most common genetic blood disorders worldwide, particularly prevalent in the Mediterranean, Middle Eastern, South Asian, and North African regions. This disease results from a reduction or defect in the production of _β globin chains, leading to abnormalities in the structure of hemoglobin. Due to the high genetic polymorphism diversity involved in this condition, a wide spectrum of clinical symptoms is observed, ranging from mild anemia to more severe manifestations. Therefore, identifying and studying the genetic polymorphisms associated with minor thalassemia is of great importance for diagnosis, disease prognosis, and the development of effective treatments. Recent studies published in the past five years have shown that polymorphisms in the α- and β-globin genes, as well as their regulatory regions, play a key role in determining disease severity and the production level of fetal hemoglobin (HbF). Increased levels of HbF are recognized as a protective factor that can alleviate the effects of anemia and mitigate disease progression. A study conducted in 2022 demonstrated that polymorphisms located in the BCL11A and HBS1L- MYB regions are directly associated with increased HbF levels in patients with minor thalassemia and can prevent the occurrence of severe symptoms. In addition, numerous genetic studies have shown that certain polymorphisms in genes regulating iron metabolism, such as HbF and TMPRSS6, can influence iron accumulation in patients with minor thalassemia and increase the risk of complications related to iron overload, such as liver fibrosis and cardiac tissue damage. These findings highlight the importance of genetic screening after the initiation of supportive treatments, especially frequent blood transfusions, and pave the way for the development of personalized therapies. Other studies have shown that genetic polymorphisms may influence the response of patients with minor thalassemia to pharmacological treatments such as hydroxyurea. Hydroxyurea is known as a fetal hemoglobin (HbF) inducer; however, its effectiveness can vary among individuals, and these differences are largely attributed to genetic polymorphisms. In addition, population-based genetic differences also play a significant role in the prevalence and types of polymorphisms. Studies conducted in various populations have shown that certain polymorphisms are more common in specific geographic regions, and these genetic variations should be considered in the design of preventive and therapeutic strategies. For instance, certain polymorphisms are more prevalent in Middle Eastern and Asian populations compared to European populations, and vice versa. Global Status of Minor Thalassemia •Global prevalence: In 2021, the age-standardized prevalence rate of thalassemia worldwide was 18.28 cases per 100,000 population. •Global mortality: The age-standardized mortality rate in 2021 was reported as 0.15 deaths per 100,000 population. •Gender differences: In most age groups, the prevalence is higher in males than in females. Regional and Country-Specific Status •Middle East and South Asia: Countries such as Iran, Iraq, and India have the highest prevalence rates of minor thalassemia. •Europe: Mediterranean countries like Greece and Italy exhibit higher prevalence of this disease. •United States: In the U.S., thalassemia-related mortality rates vary among racial groups, with Asians having the highest mortality rate. Given the heavy burden of thalassemia in many countries, especially Iran, which is one of the regions with a high prevalence of thalassemia minor, precise identification of polymorphisms and a thorough understanding of the related molecular mechanisms can be effective in improving diagnostic methods, better predicting disease progression, and developing more targeted treatments. Recent studies on polymorphisms in thalassemia minor promise significant advancements in the field of personalized medicine and targeted genetic therapies, which can markedly enhance the quality of life for patients.
  • Methods: In this study, genetic data related to beta-thalassemia minor were retrieved from the NCBI database. The extracted sequences were analyzed and processed using bioinformatics approaches. Multiple sequence alignments and phylogenetic analyses were performed using MEGA software to investigate the genetic variations and polymorphisms associated with the disease.
  • Results: The analysis identified three key genes involved in beta-thalassemia minor: HBB, HBA1, and HBA2. For each of these genes, specific single nucleotide polymorphisms (SNPs) associated with the disease were identified and thoroughly examined. Using bioinformatics approaches, the data revealed the contribution of these genes to the disease, with HBB accounting for 21.42%, HBA1 for 14.28%, and HBA2 for 64.28% of the genetic variations observed.
  • Conclusion: This study provides a comprehensive bioinformatic overview of common polymorphisms associated with beta-thalassemia minor. The findings offer a deeper understanding of the genetic basis of the disease and may contribute to the development of SNP-based diagnostic tools or targeted gene therapies in the future.
  • Keywords: Beta-Thalassemia Minor - SNPs - Hemoglobinopathy