The TNFRSF11B (OPG) 245 A>C polymorphism genetic test analyzes a specific variation in the TNFRSF11B gene, which encodes osteoprotegerin (OPG), a key regulator of bone remodeling and osteoclast activity. This test detects an adenine (A) to cytosine (C) substitution at nucleotide position 245, a genetic variation that influences OPG expression levels and function. As OPG plays a crucial role in inhibiting bone resorption by acting as a decoy receptor for receptor activator of nuclear factor-kappa B ligand (RANKL), polymorphisms in TNFRSF11B affect bone mineral density (BMD), skeletal integrity, and susceptibility to osteoporosis.
OPG is a glycoprotein that regulates bone homeostasis by binding to RANKL and preventing it from interacting with its receptor RANK on osteoclast precursors. This interaction inhibits osteoclast differentiation, reducing bone resorption and preserving bone mass. The 245 A>C polymorphism is located in a regulatory region of the TNFRSF11B gene and has been associated with differences in OPG production. Studies suggest that the C allele may lead to reduced OPG expression, increased RANKL activity, higher osteoclast numbers, and accelerated bone loss. Individuals carrying the C allele have been shown to exhibit lower BMD and an increased risk of osteoporosis-related fractures, particularly in postmenopausal women and older adults.
Bone remodeling is a dynamic process influenced by genetic and hormonal factors, with TNFRSF11B playing a central role in maintaining skeletal integrity. The 245 A>C polymorphism has been extensively studied in relation to osteoporosis and age-related bone loss, where an imbalance between bone formation and resorption contributes to skeletal fragility. Reduced OPG levels associated with the C allele may result in compromised trabecular and cortical bone structure, increasing susceptibility to fractures in weight-bearing bones such as the spine, hip, and femur. Additionally, this polymorphism has been linked to variations in peak bone mass acquisition during early adulthood, further influencing lifetime bone health.
Beyond osteoporosis, genetic variations in TNFRSF11B have been implicated in other bone-related disorders, including Paget’s disease and osteoarthritis. Dysregulation of the RANK/RANKL/OPG axis affects bone metabolism in inflammatory and degenerative conditions, contributing to pathological bone remodeling, joint degradation, and structural abnormalities. The role of OPG in vascular calcification has also been explored, as lower OPG levels have been associated with increased arterial stiffness, atherosclerosis, and cardiovascular disease risk.
Genetic testing for the TNFRSF11B (OPG) 245 A>C polymorphism provides valuable insight into an individual’s genetic predisposition to osteoporosis, bone fragility, and metabolic bone disorders.
The TNFRSF11B (OPG) 245 A>C polymorphism genetic test is also included in:
