Four genetic polymorphisms of paraoxonase gene and risk of coronary heart disease: a meta-analysis based on 88 case-control studies

Atherosclerosis. 2011 Feb;214(2):377-85. doi: 10.1016/j.atherosclerosis.2010.11.028. Epub 2010 Nov 26.

Abstract

Objective: The human paraoxonase (PON) is calcium dependent HDL associated ester hydrolase which has attracted considerable attention as a candidate gene for coronary heart disease based on its enzyme function as a key factor in lipoprotein catabolism pathways. Many studies have examined the association between polymorphisms in the PON gene and risk of coronary heart disease (CHD), but the results have been inconsistent.

Methods: We conducted a meta-analysis of 88 studies on 4 PON polymorphisms [Q192R, L55M, and T(-107)C in the PON1 and the S311C in the PON2] published before August 2010, including a total of 24,702 CHD cases and 38,232 controls. We also systematically explored potential sources of heterogeneity.

Result: In a combined analysis, the summary per-allele odds ratio for CHD of the 192R was 1.11 (95% CI: 1.05-1.17). However, when the analyses were restricted to 10 larger studies (n>500 cases), the summary per-allele odds ratio was 0.96 (95% CI: 0.90-1.02). Our analyses detected a possibility of publication bias with an overestimate of the true association by smaller studies. A meta-analysis of studies on the 55M, (-107)T, and 311C variant showed no significant overall association with CHD, yielding a per-allele odds ratio of 0.94 (95% CI: 0.88-1.00), 1.02 (95% CI: 0.91-1.15) and 1.02 (95% CI: 0.90-1.16) respectively.

Conclusions: This meta-analysis suggested an overall weak association between the R192 polymorphism and CHD risk.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aryldialkylphosphatase / genetics*
  • Case-Control Studies
  • Chi-Square Distribution
  • Coronary Disease / enzymology
  • Coronary Disease / ethnology
  • Coronary Disease / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Haplotypes
  • Heterozygote
  • Homozygote
  • Humans
  • Male
  • Odds Ratio
  • Phenotype
  • Polymorphism, Genetic*
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index

Substances

  • Aryldialkylphosphatase
  • PON1 protein, human
  • PON2 protein, human