Paraoxonase 1 polymorphisms and ischemic stroke risk: A systematic review and meta-analysis.
OBJECTIVE
Paraoxonase 1 (PON1) polymorphisms have been implicated as risk factors for coronary artery disease, but the results of genetic association studies on the related phenotype of ischemic stroke are inconclusive. We performed a meta-analysis of published studies investigating the association between ischemic stroke and two nonsynonymous PON1 polymorphisms, rs662 (p.Q192R) and rs854560 (p.L55M) in humans.


METHODS
We searched multiple electronic databases through June 30, 2009 for eligible studies. In main analyses, we calculated allele-based odds ratios with random effects models. In secondary analyses, we examined dominant and recessive genetic models as well, and performed subgroup and sensitivity analyses.


RESULTS
Regarding rs662, we identified 22 eligible studies (total of 7384 cases/11,074 controls), yielding a summary odds ratio of 1.10 per G allele (95% confidence interval, 1.04-1.17) with no evidence of between-study heterogeneity. For rs854560, 16 eligible studies (total of 5518 cases/8951 controls) yielded a summary odds ratio of 0.97 per T allele (95% confidence interval, 0.90-1.04), again with no evidence of between-study heterogeneity. For both polymorphisms, analyses with dominant and recessive genetic models yielded the same inferences as allele-based comparisons. Subgroup and sensitivity analyses showed similar results.


CONCLUSIONS
In agreement with observations in coronary artery disease, PON1 rs662 appears to be associated with a small increase in the risk of ischemic stroke.
Dahabreh
Issa J
IJ
Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, Massachusetts, USA.
Kitsios
Georgios D
GD
Kent
David M
DM
Trikalinos
Thomas A
TA
D000483:Alleles; D043303:Aryldialkylphosphatase / Q000235:genetics*; D002545:Brain Ischemia / Q000235:genetics*; D016001:Confidence Intervals; D003327:Coronary Disease / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D010641:Phenotype; D011110:Polymorphism, Genetic; D012307:Risk Factors; D020521:Stroke / Q000235:genetics*
D043303:Aryldialkylphosphatase; C468406:PON1 protein, human