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This meta-analysis confirms five FOXO3A gene polymorphisms are linked to human longevity. Notably, specific variants show a male-specific association with longer lifespans, highlighting genetic factors in aging.

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Area of Science:

  • Genetics
  • Gerontology
  • Molecular Biology

Background:

  • The FOXO3A gene, encoding the forkhead box O3 transcription factor, is implicated in human longevity.
  • Previous studies suggest associations between FOXO3A and longevity, particularly in males, but specific polymorphisms require clarification.
  • Inconclusive findings necessitate a comprehensive analysis to establish definitive links between FOXO3A variants and lifespan.

Purpose of the Study:

  • To conduct a meta-analysis clarifying the associations between specific FOXO3A gene polymorphisms and human longevity.
  • To investigate potential gender-specific effects of FOXO3A polymorphisms on longevity.
  • To consolidate evidence from existing studies for a robust statistical assessment.

Main Methods:

  • A systematic literature search identified relevant studies on FOXO3A polymorphisms and longevity.
  • Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for comparisons of minor and major alleles.
  • Meta-analysis included seven articles comprising 11 independent studies with 5241 cases and 5724 controls across diverse ethnic groups.

Main Results:

  • Five FOXO3A polymorphisms (rs2802292, rs2764264, rs13217795, rs1935949, rs2802288) were significantly associated with human longevity.
  • Gender-stratified analysis revealed significant associations for rs2802292, rs2764264, and rs13217795 with male longevity.
  • No significant associations were found for rs2802292, rs2764264, and rs1935949 with female longevity, nor for rs2153960, rs7762395, or rs13220810 with longevity overall.

Conclusions:

  • This meta-analysis confirms significant associations between five FOXO3A gene polymorphisms and human longevity.
  • The longevity-associated effects of rs2802292 and rs2764264 appear to be male-specific.
  • Further research is warranted to validate these findings and elucidate the underlying mechanisms.