Association of Xmn-1 Polymorphism with HbF Levels in Patients Presenting with Sickle Cell Disease at Tertiary Care Hospital, Karachi

Abstract

Abstract: Background: Sickle cell anemia is a common hereditary disease in Pakistan, which still maintains significant inter patient variation in disease manifestations and the reasons behind such variations remain uncertain. Among other genetic modifiers the XmnI polymorphism has been noted to influence HbF levels, response to HbF augmenting drugs and milder phenotype of disease as observed in studies conducted in various parts of world and subcontinent. XmnI polymorphism frequency and its association with HbF levels have not been investigated in Pakistani patients of sickle cell disorder. This study aims to determine different genotypes of XmnI polymorphism, and association with high HbF levels in patients of homozygous sickle and sickle/? thalassemia.
Objective: This study aimed to ascertain the association of XmnI polymorphism with HbF levels among patients with sickle cell disorders treated at Karachi's Tertiary Care Hospital.
Materials and Methods: A cross-sectional investigation was conducted at the National Institute of Blood Diseases & Bone Marrow Transplant in Karachi after obtaining approval from the Ethical Review Board bearing number IBD/RD-208/09-2020. Data collection spanned twelve months from January 01 to December 31 2021. Prospective data collection involved obtaining verbal consent from 150 patients who were diagnosed on the basis of DNA mutation analysis and fulfilled eligibility criteria. 66 sickle homozygous (HbSS) and 84 sickle ? thalassemia patients (Hb S/ß Th) were enrolled. XMN1 polymorphism analysis was performed through Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and both groups were stratified by presence of XMN-1 polymorphism i.e. homozygous (+/+), heterozy-gous (+/-) and negative (-/-) to compare frequencies of demographic factors while one-way and Welch’s ANOVA tests were applied to analyze variance among these groups.
Result: The study reported a mean age of 11.43±7.19 years and hemoglobin levels averaging 8.53±1.50 mg/dL. Gender distribution was slightly male-skewed, and ethnicity showed a predominance of individuals from Baluchistan. The frequency of XmnI polymorphism was higher in sickle homozygous patients as compared to sickle ß-thalassemia patients, significantly affecting HbF, MCV, and MCH levels. HbF levels differed across XmnI polymorphism categories, with +/+ having the highest mean. The family history of thalassemia and consanguineous marriages were more common in those with the +/- and -/- genotypes. The most common ?-globin mutation in sickle ß-thalassemia patients was found out to be IVSI-5.
Conclusion: This study concludes that XmnI polymorphism influences HbF levels of sickle cell patients in Pakistan, emphasizing the need for further comprehensive studies.