GENETIC ANALYSIS OF HEMOCHROMATOSIS AND ITS IMPACT ON LIVER FUNCTION IN THE POPULATION OF LAHORE, PAKISTAN

Abstract Hemochromatosis is an autosomal recessive iron overload disorder. Hemochromatosis occurs due to the failure of the Hepcidin response to the liver. The high level of iron in the plasma stores in the various organs and destroys the organs. It is a genetic disease. Hemochromatosis in which the HFE gene is involved is called primary hereditary hemochromatosis. The mutation in the HFE gene takes place at the p.C282Y. The methodology used in this research was organic DNA Extraction, Gel Electrophoresis, Tetra ARMS PCR, and DNA Sanger’s sequencing. The milder form of the disease, juvenile hemochromatosis (type II) is associated with mutations in either a new gene recently described as hemojuvelin 2 or antimicrobial peptide Hepcidin. Non-HFE hemochromatosis involves HJV, HAMP, TRF2, and SLC40A1 genes. 3, 4 in people with hemochromatosis, the hepcidin produced by hemojevuline, 2 and transferrin receptor 2 (TfR2) is decreased due to mutations in HFE. Typically, its expression is induced by high blood iron. Indeed, TfR2 is expressed in hepatocytes and has the 6/7 mutational pattern seen in hemochromatosis type III. This study investigates the genetic basis of hemochromatosis in the Pakistani population, focusing on the TFR2 gene variant rs7385804. It identifies a significant association between the C allele and disease susceptibility, with demographic data revealing a higher prevalence in males and onset in the mid-40s. While the study highlights the importance of genetic screening, there is a research gap in understanding the interaction between genetic and environmental factors. Future research should focus on larger, ethnically diverse samples and the development of personalized therapies. These findings could improve early diagnosis, intervention, and management of hemochromatosis, enhancing patient outcomes and quality of life. Moreover, more epidemiological work needs to be done to understand hemochromatosis's occurrence and its consequences on liver health across different populations.