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Idiosyncratic drug reactions represent abnormal chemical responses that vary significantly among individuals, ranging from extreme sensitivity to low doses to insensitivity to high doses. These reactions often occur due to the drug's covalent binding with serum proteins, forming a foreign hapten that triggers an immunotoxicological response. The variability in drug reactions has a strong pharmacogenetic foundation, with genetic differences crucial in how individuals metabolize drugs. For...
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Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
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The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...
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Genetic variation associated with hypersensitivity to mercury.

David William Austin1, Briana Spolding2, Shakuntla Gondalia3

  • 1School of Psychology, Deakin University, Victoria.

Toxicology International
|May 8, 2015
PubMed
Summary

Genetic variations in MTHFR and PON1 genes are linked to mercury sensitivity. This study identified specific polymorphisms differentiating individuals with a history of pink disease from healthy controls, shedding light on mercury hypersensitivity mechanisms.

Keywords:
Geneticsmercury sensitivitymethylenetetrahydrofolate reductaseparaoxanase 1pink disease

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Area of Science:

  • Genetics
  • Toxicology
  • Environmental Health

Background:

  • Idiosyncratic mercury (Hg) sensitivity mechanisms are poorly understood, but likely involve genetic factors.
  • Pink disease (PD) survivors represent a clinically identifiable group with heightened Hg sensitivity.

Purpose of the Study:

  • To investigate genetic variations in Hg metabolism and transport genes.
  • To compare gene polymorphisms between Hg-sensitive individuals and healthy controls.

Main Methods:

  • Single nucleotide polymorphisms (SNPs) in Hg-related genes were analyzed.
  • Comparison between PD survivors (n=25) and age/sex-matched healthy controls (n=25).

Main Results:

  • Significant differences in genotype frequencies were observed for rs662 in the paraoxonase 1 (PON1) gene.
  • Significant differences were also found for rs1801131 in the methylenetetrahydrofolate reductase (MTHFR) gene.

Conclusions:

  • Two genetic polymorphisms (in MTHFR and PON1) are associated with increased Hg sensitivity.
  • Genetic variations in MTHFR and PON1 distinguish PD survivors from healthy controls, indicating a genetic component to Hg hypersensitivity.