The CST3 gene provides instructions for making Cystatin C, a protein found throughout the human body. This protein is a cysteine protease inhibitor, produced by all nucleated cells.
Cystatin C’s General Role in the Body
Cystatin C functions as a cysteine protease inhibitor. Proteases are enzymes that break down other proteins, a process important for many cellular activities. Cysteine proteases require careful regulation.
Cystatin C inhibits these enzymes, including lysosomal proteinases that break down waste materials within cells. It is also a significant extracellular inhibitor of cysteine proteases, preventing protein breakdown outside the cell.
Cystatin C and Kidney Health
Cystatin C is a reliable biomarker for assessing kidney function, particularly for estimating the Glomerular Filtration Rate (GFR). GFR measures how well the kidneys filter waste from the blood. Unlike creatinine, Cystatin C levels are less influenced by factors such as age, sex, muscle mass, or nutritional status, making it a more consistent indicator.
Cystatin C is freely filtered by the glomeruli in the kidneys, then almost completely reabsorbed and broken down by the renal tubules. This process means that its concentration in the blood is largely dependent on the GFR. Elevated serum Cystatin C levels are strongly associated with a reduction in GFR, indicating impaired kidney function. Measuring Cystatin C in a blood sample involves immunoassays, and normal concentrations in healthy individuals range from 0.8 to 1.2 mg/L.
Cystatin C and Brain Disorders
Cystatin C also plays a role in brain health, particularly in neurodegenerative diseases like Alzheimer’s disease. Research suggests its involvement in the metabolism of amyloid-beta, a protein that can accumulate and form plaques in the brain, a hallmark of Alzheimer’s. Cystatin C has been shown to bind to amyloid-beta and reduce its aggregation and deposition.
Studies indicate that Cystatin C levels might be higher in individuals with Alzheimer’s disease. The CST3 gene itself is considered a susceptibility gene for Alzheimer’s, although not all studies have consistently confirmed this link. A specific genetic variation in the CST3 gene has been identified as a cause of hereditary cerebral amyloid angiopathy, a condition characterized by stroke and a decline in cognitive function.
Cystatin C and Cardiovascular Health
Emerging research connects Cystatin C to cardiovascular health and the risk of heart disease. Altered levels of Cystatin C have been associated with conditions such as heart failure and atherosclerosis. It has been identified as a predictor of cardiovascular events like myocardial infarction and stroke.
Lower levels of Cystatin C have been observed in individuals with coronary artery disease, and these decreased levels may correlate with the severity of the disease. While the precise mechanisms are still being investigated, an imbalance between proteinases and their inhibitors, including Cystatin C, is thought to contribute to the breakdown of vessel walls in cardiovascular conditions. This area of research continues to evolve, shedding more light on Cystatin C’s broader implications beyond kidney function.
Genetic Variations of CST3
Variations, also known as polymorphisms, within the CST3 gene can influence the levels or function of Cystatin C. The gene is located on chromosome 20 and contains the majority of type 2 cystatin genes. Several single nucleotide polymorphisms (SNPs) have been linked to changes in Cystatin C levels.
One specific variant in the CST3 gene involves a change in the protein sequence where the amino acid leucine is replaced by glutamine at position 68 (Leu68Gln or L68Q). This particular variant is associated with hereditary cerebral amyloid angiopathy, leading to a less stable Cystatin C protein that is more prone to clumping together. These genetic differences can therefore impact an individual’s susceptibility to certain diseases or affect their kidney function.