Association of TMPRSS6 (rs855791) Genetic Polymorphisms with Iron Deficiency Ane mia Risk among Sudanese Patients

ABSTRACT Background: A prevalent medical illness recognised in routine clinical practice, iron deficiency anaemia (IDA) is a global health concern. Hepcidin expression is regulated by matriptase-2 (MT-2), which is encoded by the transmembrane protease serine 6 (TMPRSS6) gene. Objective of this study was to detect the association of TMPRSS6 (rs855791) gen and iron deficiency anemia risk in Sudan. Materials and Methods: This study was carried out on 129 patients with iron deficiency anemia and 129 age and sex matched individuals as control group. Patients were subdivided into (group 1) 65 patients with acquired iron deficiency anemia (IDA) and (group 2)64 patients with iron refractory iron deficiency anemia (IRIDA). TMPRSS6 gene single nucleotide polymorphisms(SNPS), (rs855791&) was evaluated using real time – polymerase chain reaction (RT-PCR) while serum iron profile was measured by enzyme linked immunosorbent assay (ELISA). Results: Among 129 patients, 68 were male (mean age: 12.2 ± 4.3 years) and 61 were female (mean age: 12.1 ± 5.6 years). In addition, 129 healthy age-matched and sex-matched individuals served as controls.  The (mean ±SD) of HB, Hematocrit, MCV, MCH and MCHC were significantly deceased in both case group compared to control group (p vale =0.01, 0.03, 0.01, 0.01, 0.0483) and were insignificant relation between two groups in mean ±SD of WBCs, RBCs, RDW and PLT. Serum iron, total iron-binding capacity (TIBC), and ferritin levels showed a significant reduction in patient groups compared to controls (p-values: 0.015, 0.044, and 0.020). As regard SNP rs 855791, there was a significant increase in frequency of mutations (heterozygous and homozygous) in IDA group compared to control group (p=0.025) and highly significant increase in frequency of mutations (heterozygous and homozygous) in IRIDA group compared to control group (p=0.001) and compared to IDA group (p=0.003).  Conclusion: The study demonstrates a significant reduction in hematological and iron profile parameters in both IDA and IRIDA patients compared to controls, with IRIDA patients showing the most pronounced deficiency. Additionally, IRIDA patients exhibited a highly significant increase in mutation frequency compared to both IDA patients and controls, suggesting a distinct genetic influence on iron metabolism.