Molecular Characterisation of Genes Involved in Iron Homeostasis

The overall aim of this study was to identify the role of genetic variants and mutations in association with different iron related disorders. There is a radical change in understanding iron metabolism and its regulation over the past few years after the discovery of iron regulatory hormone hepcidin and its regulator matriptase-2. Iron homeostasis and dysregulation is inevitably an intricate phenomenon necessitating an extensive research to unfold its complexity. Here we attempted to understand the biology and other molecular indicators of distinctive conditions where the iron homeostasis is disturbed. We included patients with either iron deficiency or iron overload to perceive a broad perspective of molecular basis of iron dysregulation. We undertook experiments to understand the expression of various genes in iron metabolism under different iron status. We also evaluated the expression and possible role of GDF15 in iron regulation. 1. Iron deficiency anemia and iron overload: • Our study demonstrates that iron deficiency anemia still remains a major health issue in our population affecting predominantly children and pregnant women. Inspite of various interventions and management programmes to control iron deficiency anemia it continues to be one of the major contributor of anemia. • Low socioeconomic background is thought to be one of the major causes of iron deficiency; but our findings in this study contradict this popular notion. In our study, only 27% of subjects with IDA belonged to lower socioeconomic status. • Three variants rs3811647 (TF), rs34242818 (TFR2), rs200434923 (TMPRSS6), are significantly associated with low ferritin in patients with iron deficiency anemia in our study; these variants have not been associated with ferritin in previous studies implying that the role of genetic variants in modulating iron status may vary in populations. • An important observation seen in this study was genetic variants in iron related genes influence iron absorption. This is evident from the significant difference in allelic frequency of variants between patients with poor and good iron absorption after oral iron challenge. • This is the first report from India highlighting the importance of genetic screening in patients with atypical anaemia. Six percent of patients with anemia had atypical characteristics and mutations in iron related genes. These mutations resulted in defective function in iron related proteins (TMPRSS6, CP, TF) blocking iron entry into circulation and different tissues. • Anemia during pregnancy was not severe but a small proportion of subjects (3.7%) had severe anemia (Hb