The VDR 2 A>G (Lys2Arg) [FokI] polymorphism genetic test analyzes a specific variation in the VDR gene, which encodes the vitamin D receptor (VDR), a nuclear transcription factor responsible for mediating the biological effects of vitamin D. This test detects an adenine (A) to guanine (G) substitution at the start codon of the VDR gene, resulting in an amino acid change from lysine (Lys) to arginine (Arg) at position 2. This polymorphism influences the functional activity of VDR by altering the length of the receptor protein, affecting its ability to regulate calcium homeostasis, bone mineral density (BMD), immune responses, and metabolic processes.
VDR is a key regulator of calcium and phosphate metabolism, facilitating the effects of active vitamin D (1,25-dihydroxyvitamin D3) on target tissues, including bone, intestines, kidneys, and the immune system. The VDR FokI polymorphism affects the efficiency of VDR-mediated gene transcription, with studies indicating that the G allele results in a shorter, more transcriptionally active receptor variant. The A allele encodes a longer VDR protein, which has been associated with lower receptor efficiency, reduced calcium absorption, and alterations in bone metabolism. Individuals carrying the A allele may exhibit lower BMD and an increased risk of osteoporosis-related fractures, particularly in postmenopausal women and aging individuals, while those with the G allele may have a more efficient response to vitamin D.
Bone health is significantly influenced by VDR activity, as calcium absorption and bone remodeling are regulated by vitamin D signaling. Variations in VDR contribute to individual differences in skeletal integrity, peak bone mass acquisition, and susceptibility to bone loss over time. Research has linked the FokI polymorphism to osteoporosis risk, with the A allele being more prevalent in individuals with reduced bone density. Additionally, this polymorphism has been associated with differences in response to vitamin D supplementation and calcium intake, further highlighting its role in skeletal health.
Beyond bone metabolism, the VDR 2 A>G (Lys2Arg) polymorphism has been implicated in immune system regulation, given the role of vitamin D in modulating immune responses. Studies suggest that the A allele may be linked to an increased risk of autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, and type 1 diabetes, due to alterations in immune cell activation and inflammatory processes. The efficiency of vitamin D-mediated immunomodulation may differ between genetic variants, influencing susceptibility to chronic inflammatory conditions.
VDR function also affects cardiovascular and metabolic health, with polymorphisms such as FokI playing a role in insulin sensitivity, lipid metabolism, and blood pressure regulation. The A allele has been associated with an increased risk of type 2 diabetes, obesity, and hypertension, while the G allele may contribute to improved glucose metabolism and cardiovascular protection. Variability in VDR function influences the effectiveness of vitamin D in maintaining metabolic balance, impacting overall health outcomes.
Genetic testing for the VDR 2 A>G (Lys2Arg) [FokI] polymorphism provides insight into an individual’s genetic predisposition to osteoporosis, immune-related disorders, and metabolic conditions. Identifying this variant allows for assessing calcium and vitamin D metabolism, skeletal health, and immune function.
The VDR 2 A>G (Lys2Arg) [FokI] polymorphism genetic test is also included in:
