Introduction:- Osteoporosis is a multifactorial disease whose interaction between genetic and environmental factors lead to a reduction of bone mineral density accompanied by
changes in bone microarchitecture level, leading to a significant decrease in bone strength and an increased fracture risk.
- Iron is known to play a relevant role in the development of osteoporosis as it suppresses osteoblast formation and may also stimulate osteoclast resorption of bone.
As so, polymorphisms in genes affecting iron homeostasis can increase the susceptibility for the development of osteoporosis.
- HFE is a major histocompatibility complex class I-like protein which gene is commonly mutated in Hereditary Hemochromatosis, a disorder characterized by excessive
intestinal iron absorption and its deposition in several organs. It has been postulated that HFE may contribute to iron metabolism regulation by activating hepcidin
synthesis in hepatocytes and regulating the expression of iron metabolism-related genes (ferroportin) in duodenum and other cells. - The locus encoding HFE is located on the long arm of chromosome 6 (6q22.2) and contains 2 major polymorphisms. A 845G-A transition resulting in a cys282-to-tyr
(C282Y) substitution and a C-to-G transversion in exon 2 resulting in a his63-to-asp substitution (H63D).
- Haptoglobin (Hp) is an acute phase protein that binds free hemoglobin (Hb) released from erythrocytes with high affinity and thereby inhibits its oxidative activity.
- The locus encoding haptoglobin is located on the long arm of chromosome 16 (16q22.2) and presents a copy number variation polymorphism (CNV) that results from
an internal duplication of a gene segment (exons 3 and 4). This gives rise to three different genotypes (Hp1.1, Hp 2.1 and Hp2.2) that modulate the half-life of Hp-Hb
complex, its plasma concentration as well as other functions (angiogenesis, immune, etc
