The TNFRSF11B (OPG) A>G (rs4355801) polymorphism genetic test analyzes a specific variation in the TNFRSF11B gene, which encodes osteoprotegerin (OPG), a key regulator of bone metabolism and osteoclast inhibition. This test detects an adenine (A) to guanine (G) substitution at the rs4355801 locus, a genetic variation associated with differences in bone mineral density (BMD), skeletal strength, and susceptibility to osteoporosis. As OPG functions as a decoy receptor for receptor activator of nuclear factor-kappa B ligand (RANKL), variations affecting its expression or activity influence bone resorption, remodeling, and overall skeletal integrity.
OPG plays a crucial role in regulating bone homeostasis by preventing RANKL from binding to its receptor RANK on osteoclast precursors. This inhibition limits osteoclast differentiation and activity, reducing bone resorption and maintaining bone density. The rs4355801 polymorphism, located near regulatory elements of the TNFRSF11B gene, has been associated with altered OPG expression levels, leading to differences in osteoclast-mediated bone breakdown. Studies suggest that the G allele is correlated with lower OPG expression, resulting in increased osteoclast activity, higher bone turnover rates, and reduced BMD. Carriers of the G allele have been shown to exhibit a greater risk of osteoporosis and fragility fractures, particularly in postmenopausal women and aging individuals.
The TNFRSF11B A>G polymorphism has been extensively studied in relation to osteoporosis, a condition characterized by progressive bone loss and an increased risk of fractures. The genetic influence of this polymorphism on BMD suggests that individuals with the G allele may experience accelerated bone deterioration, particularly in weight-bearing bones such as the spine, hip, and femur. Research has also linked this polymorphism to peak bone mass acquisition in younger populations, indicating its role in determining lifetime skeletal health. Variations in TNFRSF11B may contribute to individual differences in response to dietary calcium, vitamin D intake, and mechanical loading, further influencing bone metabolism and fracture risk.
Beyond osteoporosis, the TNFRSF11B A>G polymorphism has been implicated in other skeletal and metabolic conditions, including osteoarthritis and vascular calcification. OPG prevents pathological calcification in arterial walls, and reduced OPG levels have been associated with an increased risk of atherosclerosis, arterial stiffness, and cardiovascular disease. Additionally, variations in TNFRSF11B have been linked to inflammatory bone diseases such as rheumatoid arthritis, where dysregulated osteoclast activity contributes to joint destruction and bone erosion.
Genetic testing for the TNFRSF11B (OPG) A>G (rs4355801) polymorphism provides valuable insight into an individual’s genetic predisposition to osteoporosis, bone fragility, and metabolic bone disorders. Identifying this variant allows for assessing bone resorption activity and skeletal health, contributing to a deeper understanding of bone metabolism and fracture susceptibility.
The TNFRSF11B (OPG) A>G (rs4355801) polymorphism genetic test is also included in:
