Calcium in blood gene casr
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Calcium-Sensing Receptor (CASR) Gene and Its Role in Blood Calcium Regulation
Introduction to CASR and Blood Calcium Regulation
The calcium-sensing receptor (CASR) gene plays a crucial role in maintaining extracellular calcium homeostasis. CASR is a G-protein-coupled receptor that detects changes in blood calcium levels and modulates parathyroid hormone (PTH) secretion and renal calcium excretion to maintain calcium balance . This receptor is encoded by the CASR gene located on chromosome 3q21.1 and consists of 1078 amino acids.
Genetic Variations and Their Impact on Calcium Levels
Common Polymorphisms and SNPs
Genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) near the CASR gene that significantly affect serum calcium levels. For instance, the SNP rs1801725 has been shown to explain 1.26% of the variance in serum calcium levels in individuals of European descent. Another common polymorphism, A986S, has been associated with higher serum calcium levels and is considered a genetic determinant of extracellular calcium concentration.
Inherited Mutations and Disorders
Mutations in the CASR gene can lead to various inherited disorders of calcium metabolism. Loss-of-function mutations result in hypercalcemic conditions such as familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism, while gain-of-function mutations cause hypocalcemic disorders like autosomal dominant hypocalcemia (ADH) . These mutations alter the receptor's ability to sense and respond to calcium levels, leading to abnormal PTH secretion and calcium handling by the kidneys.
Clinical Implications of CASR Mutations
Diagnostic and Therapeutic Considerations
Molecular diagnosis of CASR mutations is essential for accurately diagnosing and managing calcium metabolism disorders. Genetic screening can identify specific mutations, which helps in distinguishing CASR-related conditions from other similar disorders . For example, patients with inactivating mutations often present with hypercalcemia and normal or elevated PTH levels, while those with activating mutations exhibit hypocalcemia and low PTH levels.
Treatment Strategies
Treatment of CASR-related disorders varies depending on the type of mutation. For hypercalcemic conditions, calcimimetics like cinacalcet can be used to activate the CASR and reduce PTH secretion. Conversely, calcilytics, which inhibit the CASR, may be beneficial for treating hypocalcemic conditions. However, managing these conditions requires careful monitoring to avoid complications such as nephrocalcinosis and nephrolithiasis, especially in patients with ADH1.
Conclusion
The CASR gene is pivotal in regulating blood calcium levels through its role in PTH secretion and renal calcium excretion. Genetic variations, including common polymorphisms and inherited mutations, significantly impact calcium homeostasis and can lead to various hypercalcemic and hypocalcemic disorders. Molecular diagnosis and targeted therapies are crucial for managing these conditions effectively, highlighting the importance of understanding CASR's genetic and functional landscape.
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