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Association between three common genetic polymorphisms of XPC and susceptibility to heroin dependency

Akram Qasemian-Talgard1, Mostafa Saadat1

  • 1Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran.

Gene
|October 15, 2019
PubMed

Insights

Genetic variations in the Xeroderma pigmentosum complementation group C (XPC) gene did not influence heroin dependency risk. However, specific XPC haplotypes and diplotypes were linked to increased risk and earlier age of first drug use, respectively.

Area of Science:

  • Genetics
  • Neuroscience
  • Toxicology

Background:

  • Opioid use, including heroin and morphine, induces oxidative stress and DNA damage in neurons.
  • The Xeroderma pigmentosum complementation group C (XPC) gene plays a crucial role in DNA repair via the nucleotide excision repair pathway.
  • Common XPC polymorphisms (Lys939Gln, Ala499Val, PAT) are known to impair DNA repair capacity.

Purpose of the Study:

  • To investigate the association between XPC gene polymorphisms and the risk of heroin dependency (HD).
  • To examine the relationship between XPC polymorphisms and the age of first use (AFU) of illegal drugs.

Main Methods:

  • Genotyping of three common XPC polymorphisms in 795 healthy individuals and 442 heroin-dependent patients.
  • Statistical analysis including haplotypic and diplotypic comparisons.
  • Cox proportional hazard models were used to assess the association with AFU.

Main Results:

  • No significant association was found between individual XPC polymorphisms and the risk of HD.
  • Significant differences in XPC haplotypic frequencies were observed between HD patients and controls.
  • The 'Ala + Gln' haplotype was associated with increased HD risk, while the 'Val - Lys/Val - Lys' diplotype correlated with a lower AFU.

Conclusions:

  • XPC gene polymorphisms do not appear to be a major risk factor for developing heroin dependency.
  • Specific XPC haplotypes may influence heroin dependency risk.
  • XPC gene variations, particularly the Ala499Val polymorphism and related diplotypes, are associated with the age of first drug use, suggesting a role in initiation of substance use.
Keywords:
Drug dependencyGenetic polymorphismXPC

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