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Related Experiment Videos

Paraoxonase 1 polymorphisms and survival.

L Christiansen1, L Bathum, H Frederiksen

  • 1Epidemiology, Institute of Public Health, University of Southern Denmark, Odense, Denmark. lchristiansen@health.sdu.dk

European Journal of Human Genetics : EJHG
|July 9, 2004
PubMed
Summary

Paraoxonase 1 (PON1) 192RR homozygosity is linked to increased mortality in women over 47, particularly concerning survival after coronary heart disease (CHD), not initial susceptibility.

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Area of Science:

  • Genetics
  • Cardiovascular Disease
  • Longevity Research

Background:

  • Paraoxonase 1 (PON1) is an antioxidant enzyme linked to protection against coronary heart disease (CHD).
  • Genetic variations in PON1, including polymorphisms 55M/L, 192Q/R, and -107C/T, have been studied for their association with CHD susceptibility.
  • The impact of these PON1 polymorphisms on overall mortality requires further investigation.

Purpose of the Study:

  • To investigate the impact of three common PON1 polymorphisms (55M/L, 192Q/R, -107C/T) on mortality in a Danish cohort.
  • To examine the association between PON1 genotype and haplotype distributions and survival rates.
  • To evaluate the role of the PON1 192Q/R polymorphism in susceptibility to and survival after coronary heart disease.

Main Methods:

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  • Utilized a sample of 1932 Danish individuals (aged 47-93 years) for cross-sectional and longitudinal follow-up studies.
  • Analyzed genotype and haplotype distributions for PON1 55M/L, 192Q/R, and -107C/T polymorphisms across different age groups.
  • Confirmed findings in an independent sample of 541 Danish individuals, focusing on survival analysis and self-reported ischemic heart disease data.

    • Main Results:

    • No significant differences in genotype or haplotype distributions were found in cross-sectional analyses.
    • Longitudinal follow-up revealed that PON1 192RR homozygotes had poorer survival compared to QQ homozygotes (HR: 1.38, P=0.04), an effect confirmed in an independent cohort.
    • The association between 192RR homozygosity and increased mortality was most pronounced in women and appeared related to CHD survival rather than susceptibility.

    Conclusions:

    • PON1 192RR homozygosity is associated with increased all-cause mortality in women in the second half of life.
    • This increased mortality risk may be linked to survival after coronary heart disease (CHD) rather than the initial development of CHD.
    • The findings highlight a potential sex-specific role of PON1 genotype in cardiovascular health and longevity.