The HBG2 rs7482144 (C > T) Polymorphism is Linked to HbF Levels but not to the Severity of Sickle Cell Anemia

Abstract

Sickle cell anemia (SCA) is a severe disease characterized by anemia, acute clinical complications, and a relatively short life span. In this disease, abnormal hemoglobin makes the red blood cells deformed, rigid, and sticky. Fetal hemoglobin (HbF) is one of the key modulators of SCA morbidity and mortality. Interindividual HbF variation is a heritable trait that is controlled by polymorphism in genes linked and unlinked to the hemoglobin β gene (HBB). The genetic polymorphisms that determine HbF levels are known to ameliorate acute clinical events. About 190 well-characterized homozygous SCA patients were included in this study. Complete blood count (CBC), high-performance liquid chromatography (HPLC), and clinical investigations were obtained from patient's records. Severity scores were determined by using the combination of anemia, complications, total leucocyte count, and transfusion scores. HBG2 rs7482144 polymorphism was genotyped by using the polymerase chain reaction and restriction fragment length polymorphism. The association between HBG2 rs7482144 polymorphism and HbF levels as well as the disease severity of SCA were assessed. SCA patients carrying TT genotype were found to have higher HbF levels. In addition, SCA patients with increased severity showed significantly lower levels of hemoglobin, HbF, and hematocrit values. However, the genotypes of HBG2 rs7482144 polymorphism were not found to be associated with the risk of disease severity. In summary, this study demonstrated that HBG2 rs7482144 polymorphism is linked with HbF levels, but it does not affect disease severity. The sample sizes used and the pattern of association deduced from our small sample size prevents us from extrapolating our findings further.

Infection and Potential Challenge of Childhood Mortality in Sickle Cell Disease: A Comprehensive Review of the Literature from a Global Perspective

“…Hydroxyurea administration may be one of the most effective ways to reduce complications such as VOC during SARS-CoV-2. The HBG2 rs7482144 (C > T) polymorphism, on the other hand, is linked to HbF levels but not to the severity of SCD [165]. The use of antimalarial drugs, specifically hydroxychloroquine, has been linked to side effects in SCD patients, such as ventricular arrhythmias and cardiac toxicity, as reported in other COVID-19 patients [166].…”

Risk Association, Linkage Disequilibrium, and Haplotype Analyses of β-Like Globin Gene Polymorphisms with Malaria Risk in the Sabah Population of Malaysian Borneo

“…Variants in a human gene are regularly associated with the risk of certain diseases. For example, the C-158T (rs7482144) single nucleotide polymorphism (SNP) in the 5′ region of the hemoglobin subunit gamma 2 gene is linked with higher fetal hemoglobin levels, sickle cell anemia, and thalassemia [ 7 , 8 ]. Interestingly, another SNP in the 5′ region of the β-globin gene, the C-551T (rs number is not available), is found as a silencer for the gene’s transcription and is associated with a thalassemic phenotype [ 9 ].…”