The Impact of Single Nucleotide Polymorphisms and Other Mechanisms on Aspirin Resistance

Natalia Sergeevna Nuzhdina1, Aleksei Vitalievich Kurguzov1, David Sergeevich Sergeevichev1

  • 1E. Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation, Rechkunovskaya Str., 15, 630055 Novosibirsk, Russia.

Insights

Aspirin resistance (AR) varies widely, impacting treatment effectiveness for cardiovascular diseases. Genetic variations (SNPs) in key genes may explain inconsistent responses to antiplatelet therapy, necessitating careful interpretation of genotyping results.

Area of Science:

  • Cardiovascular Medicine
  • Pharmacogenomics
  • Molecular Biology

Background:

  • Atherosclerosis and ischemic events are central to cardiovascular diseases (CVD).
  • Antiplatelet agents are crucial for preventing thrombosis post-cardiovascular surgery.
  • Current aspirin and dual antiplatelet therapies show controversial effectiveness, with some patients exhibiting aspirin resistance (AR).

Purpose of the Study:

  • To review scientific literature on detecting and genotyping single nucleotide polymorphisms (SNPs) in genes related to aspirin's therapeutic targets.
  • To explore the association between SNPs and aspirin resistance (AR) or high platelet reactivity (HPR) in patients with ischemic heart disease (IHD).

Main Methods:

  • Literature review of studies on experimental detection and genotyping of SNPs.
  • Analysis of SNPs in key therapeutic target genes: COX-1, COX-2, GUCY1A3, GPIIb-IIIa, and PEAR1.
  • Examination of SNP distribution in patients with IHD and control groups.

Main Results:

  • Aspirin resistance (AR) prevalence ranges from 0% to 66% in IHD patients and controls.
  • SNP analysis is proposed to explain high platelet reactivity (HPR) in patients on aspirin therapy.
  • The efficacy of aspirin in secondary thrombosis prevention is not strongly linked to known SNPs, with inconsistent clinical trial results.

Conclusions:

  • The inconsistent efficacy of aspirin therapy in preventing recurrent cardiovascular thrombotic events may be linked to genetic variations (SNPs).
  • Methodological and quantitative issues in clinical trials contribute to conflicting results regarding AR and SNPs.
  • Careful interpretation of SNP genotyping is essential for understanding aspirin's effectiveness in CVD patients.

Related Concept Videos

Single Nucleotide Polymorphisms-SNPs01:05

Single Nucleotide Polymorphisms-SNPs

A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
13.7K
Factors Affecting Protein-Drug Binding: Drug Interactions01:23

Factors Affecting Protein-Drug Binding: Drug Interactions

Drug interactions are a critical aspect of pharmacology and can occur when two or more drugs compete for the same binding site. This competition can result in one drug displacing another, altering the effect of the displaced drug. Drug interactions are complex processes that rely heavily on how much of the displacer drug is present and how strongly it can bind to the same sites as the displaced drug.
Displacement interactions can have varying outcomes, ranging from toxicity to virtually...
71
Factors Affecting Drug Biotransformation: Biological01:19

Factors Affecting Drug Biotransformation: Biological

Biological factors significantly impact drug metabolism, influencing drug clearance, efficacy, and potential toxicity.
Species differences: Variations in enzyme systems across species can cause disparities in drug metabolism. For instance, humans may metabolize certain drugs faster than rodents, altering therapeutic effects.
Strain differences: Genetic variations within a species can result in differing enzyme activity, impacting drug response and toxicity. For example, some mouse strains may...
83
Genome-wide Association Studies-GWAS01:11

Genome-wide Association Studies-GWAS

Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
12.2K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.2K
Genome Copying Errors02:46

Genome Copying Errors

DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their  survival. Therefore, the copying errors are checked and repaired at three levels.
4.1K