The association between apolipoprotein E gene polymorphisms and essential hypertension: a meta-analysis of 45 studies including 13,940 cases and 16,364 controls

J Hum Hypertens. 2013 Apr;27(4):245-55. doi: 10.1038/jhh.2012.37. Epub 2012 Sep 13.


The apolipoprotein E single-nucleotide polymorphisms are among the potential candidate genes that may serve as modulators in susceptibility to essential hypertension. In an effort to clarify earlier inconclusive results, we performed a meta-analysis of population-based case-control genetic association studies. Random-effects methods were applied on summary data in order to combine the results of the individual studies. We identified in total 45 studies, including 13 940 hypertensive cases and 16 364 controls. The contrast of E4 carriers versus non-carriers yielded an overall odds ratio (OR) of 1.16 (95% confidence interval (CI): 1.02, 1.31), whereas the contrast of E4 allele versus the others in a subtotal of 6617 cases and 7330 controls, yielded an OR of 1.39 (95% CI: 1.12, 1.72). There was moderate evidence of publication bias in both contrasts, which was eliminated after excluding studies not in Hardy-Weinberg equilibrium. Subgroup analyses revealed that significant estimates arose from studies on Asian populations, as opposed to the Caucasian ones. Furthermore, no evidence of publication bias was demonstrated in the comparisons within this subgroup. Our results are consistent with recent meta-analyses but show that the association is weaker than that has been previously demonstrated. Further studies are needed in order to fully address questions about the etiological mechanism of the particular association, as well as to study the effect in populations of African descent.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apolipoproteins E / blood
  • Apolipoproteins E / genetics*
  • Blood Pressure / genetics*
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Hypertension / blood
  • Hypertension / ethnology
  • Hypertension / genetics*
  • Hypertension / physiopathology
  • Male
  • Middle Aged
  • Odds Ratio
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Risk Assessment
  • Risk Factors


  • Apolipoproteins E