The effect of the XMN۱-HBG۲ (rs۷۴۸۲۱۴۴) single nucleotide polymorphism on fetalhemoglobin in β-thalassemia intermedia patients: a systematic review

Introduction: Thalassemia is a genetic disorder causing abnormal hemoglobin production, leading to anemia.It is prevalent in Iran and can be mild, intermediate, or severe. Patients with β-thalassemia intermedia (β-TI)have a milder form of the disease than those with severe β-thalassemia. Increased fetal hemoglobin (HbF) levelsdecrease clinical symptoms in β-thalassemia patients. The XMN۱-HBG۲ gene regulates HbF expression. Theaim of this review study is to investigate the association between XMN۱-HBG۲ single nucleotide polymorphism(SNP) rs۷۴۸۲۱۴۴, variation in HbF levels, and anemia severity in β-TI patients.Methods: Based on Cochrane systematic review principles and PRISMA guidelines, the study was conductedusing keywords such as "rs۷۴۸۲۱۴۴," "β-thalassemia," and "fetal hemoglobin" in databases such as Scopus,PubMed, and Web of Science. The Google Scholar search engine has been used for reviewing gray literature.These searches were conducted from ۲۰۱۰ to ۲۰۲۳ in the databases. The inclusion criteria were Englishlanguagestudies that investigated the association of the rs۷۴۸۲۱۴۴ SNP with HbF level in β-TI patients. Theexclusion criteria were non-English language articles, review and animal studies, and conference articles. Twoauthors independently conducted screening and data extraction, with a third author's consensus on discrepancies.Quality assessment was done using the Cochrane ROB ۲ tool, and data was collected in extraction tables.Results: Overall, ۷۲۵ articles were found, and after removing ۷۰۴ duplicates and irrelevant titles and abstracts,the full text of ۲۱ articles was assessed for eligibility. Finally, ۴ studies met the inclusion criteria with ۲۶۲ β-TIpatients. Studies have been conducted on the populations of Iraq, Iran, Pakistan, and France. The HBG۲rs۷۴۸۲۱۴۴ polymorphism results from a C-to-T nucleotide substitution at position ۱۵۸ of the γ-globin gene.HbF levels were primarily influenced by the allele of rs۷۴۸۲۱۴۴ (Xmn۱-HBG۲). The results showed that thers۷۴۸۲۱۴۴ SNP has a significant association with increasing HbF levels and decreasing the severity of anemiain β-TI patients (p<۰.۰۵). The presence of the HBG۲ rs۷۴۸۲۱۴۴ "T" allele in β-thalassemia patients is correlatedwith significantly higher mean HbF as compared with patients with the "C" allele.Conclusion: Studies indicate a significant correlation between XMN۱-HBG۲ (rs۷۴۸۲۱۴۴) single nucleotidepolymorphism, increased HbF levels, and decreased anemia severity in β-TI patients. However, due to limitedstudies and heterogeneity, further research is needed to confirm these findings. This review offers valuableinsights for researchers and clinicians studying the genetic determinants of β-thalassemia intermedia.

کلیدواژه ها:

β-Thalassemia intermedia ، Fetal hemoglobin ، single nucleotide polymorphism ، XMN۱-HBG۲