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Diverse genes, unexpected responses: Why do some people respond so differently to clagadin?
With the rapid development of modern medicine and the demand for personalized medicine, how genes affect drug response has become a hot research topic. Among them, the variation of cytochrome P450 2C19 (CYP2C19 for short) enzyme has attracted widespread attention in the scientific community because this enzyme has rare variation in 15% to 20% of Asians, which makes these people respond to commonly used drugs with completely different results.
CYP2C19 is one of the most important drug-metabolizing enzymes in the liver, responsible for metabolizing at least 10% of clinical drugs.
Genetic polymorphisms in this enzyme result in individual differences in the ability to metabolize drugs, which may lead to unexpected responses in patients when receiving drug treatment. For example, the commonly used antiplatelet drug clopidogrel is particularly dependent on CYP2C19. Clagertine itself is a prodrug that must be converted into an active form through metabolism by CYP2C19 to exert its efficacy. This means that people carrying the CYP2C19 mutation may not achieve the expected therapeutic effect due to decreased metabolic capacity, and may even increase the risk of major cardiovascular events.
The study pointed out that mutations such as CYP2C19*2 and CYP2C19*3 would reduce the efficacy of clagadin, and the relative risk of cardiovascular events in these patients was increased by 1.53 to 3.69 times compared with patients who did not carry the gene mutation.
Specifically, the CYP2C19 gene has multiple variations that affect the ability to metabolize drugs. The most common is CYP2C19*1 (wild type), which is usually normal. In contrast, CYP2C19*2 and CYP2C19*3 are considered loss-of-function alleles, resulting in reduced metabolic capacity, while CYP2C19*17 is a gain-of-function allele, which increases enzyme activity. This means that patients with different genotypes may experience completely different drug responses when receiving the same drug treatment.
The findings highlight the value of pharmacogenomics, which allows healthcare providers to tailor medication plans based on a patient's genotype to improve efficacy and reduce side effects. For example, for patients with CYP2C19*2 or *3 variants, doctors may consider using other antiplatelet drugs that are not dependent on CYP2C19 metabolism, such as ticagrelor, to achieve better therapeutic effects.
It was reported that a 2021 study showed that ticagrelor had better efficacy than clagadin in patients with CYP2C19 dysfunction.
However, for patients with the CYP2C19*17 gene variant, although this variant helps to increase the metabolic rate and increase the response to certain drugs, it may also cause unwanted side effects. For example, high doses of antidepressant medications may not be as effective in these patients and therefore require more careful monitoring and dosage adjustments.
Different people may have completely different reactions to drugs due to their different genotypes. This is frequently seen in clinical trials, but more research is needed into the underlying mechanisms of these variations to better understand their impact on drug action. If a gene variant may be the reason why some patients cannot effectively respond to drugs, how should we adjust our drug strategies to cater to the needs of different patients?
