Investigation of the effect of SNPs affecting HbF level on hemoglobinopathy clinic in patients with β-thalassemia major in Çukurova region

Hemoglobinopathy is the most common group of monogenic disorders with autosomal recessive inheritance. It is characterized by mutations or deletions in the genes encoding the alpha (α) and beta (β) globin chains of the hemoglobin (Hb) molecule. It is among the most common inherited blood diseases in our country and is an important health problem especially in the south and west regions. In the studies conducted, it is known that thalassemia carriage is 3% and the incidence of sickle cells is 10% in Çukurova Region. In recent years, single gene polymorphisms (SNPs) have been used with increasing interest in determining the genetic variation in the responses of individuals to drugs in complex diseases, developing individual treatment options according to the patient's genotype and determining new therapeutic targets. Fetal hemoglobin (HbF) level rises in different amounts in hemoglobinopathies such as β- thalassemia and sickle cell anemia (HbS). The continuation of HbF at varying levels in adulthood is controlled by genetic factors. Among these factors, there are QTL (Quantitative Trait Loci) containing BCL11A on chromosome 2, HMIP SNPs on chromosome 6. Together, these SNPs make up about half of the change in HbF levels. In our study, the clinical severity BCL11A and HMIP SNPs and gamma globin gene expression levels in 100 patients with β-thalassemia and sickle cell anemia who were admitted to the Pediatric Hematology Department and received blood transfusion by increasing HbF synthesis. In our study, rs1427407 (BCL11A) and rs9399137 (HMIP) SNPs, which improved the phenotype by increasing HbF synthesis in 90 patients with β-thalassemia and 10 sickle cell anemia, who applied to the Department of Pediatric Hematology, were used by using RT-PCR methods. Patients were evaluated with 51% "C/C, 21% "C/T" and 28"T/T" alleles in rs1427407 polymorphism. Alleles and 100% of the patients in the rs9399137 polymorphism were found to carry the "T/T" allele. The allele frequencies of the two SNPs screened in the patients were examined and rs1427407 "C" and rs9399137 "T" alleles were determined as major alleles. When the rs1427407 and rs9399137 polymorphisms were examined together, it was determined that HbF synthesis was high (p<0.001) in individuals carrying the rs1427407 "C/T" and rs9399137 "T/T" alleles together. It was found that the rs1427407 polymorphism affected HbF levels more in patients with β-thalassemia with the "C/T" genotype compared to individuals with SCA (p<0.001).