To the editor,

I have read with interest the recent report by Liu and coworkers on the role of paraoxonase (PON) genes in ischemic stroke [1]. Based on 28 studies, the authors conclude to a risk-enhancing effect of a PON1 missense substitution, Q192R, and to nonsignificant effects of other paraoxonase gene variants. It would appear, however, that the data assembled do not reflect the existing evidence and, therefore, offer a distorted view of the role played by PON genes in the phenotype under study. Liu et al. do not specify the data freeze for including studies in their analysis but a rapid search disclosed multiple investigations that were omitted, e.g., for Q192R, Topić et al. [2], Voetsch et al. [3], and Ranade et al. [4], to name only a few. Intriguingly, a number of other studies were first retrieved by Liu et al. but were then overlooked in the analysis, e.g., for Q192R, references 34 and 36 were dropped. Likewise, for PON1 L55M, data are missing from references 41 and 46. For PON2 G148A, data are missing from reference 53 which identifies G as the major allele leading to a substantial shift in the overall risk. The figures given for PON2 C311S are grossly in error in that the protective and at-risk alleles were muddled for references 46 and 52 in table 2. Moreover, several large investigations are again missing, e.g., Wang et al. [5]. On the whole, the above flaws call for a cautious stand on the proposed contribution made by PON genes to augmenting the risk for ischaemic stroke.


  1. Top of page
  2. References
  • 1
    Liu H, Xia P, Liu M et al. PON gene polymorphisms and ischaemic stroke: a systematic review and meta analysis. Int J Stroke 2013; 8:111123.
  • 2
    Topić E, Simundić AM, Ttefanović M et al. Polymorphism of apoprotein E (APOE), methylenetetrahydrofolate reductase (MTHFR) and paraoxonase (PON1) genes in patients with cerebrovascular disease. Clin Chem Lab Med 2001; 39:346350.
  • 3
    Voetsch B, Benke KS, Panhuysen CI et al. The combined effect of paraoxonase promoter and coding region polymorphisms on the risk of arterial ischemic stroke among young adults. Arch Neurol 2004; 61:351356.
  • 4
    Ranade K, Kirchgessner TG, Iakoubova OA et al. Evaluation of the paraoxonases as candidate genes for stroke: Gln192Arg polymorphism in the paraoxonase 1 gene is associated with increased risk of stroke. Stroke 2005; 36:23462350.
  • 5
    Wang X, Cheng S, Brophy VH et al. A meta-analysis of candidate gene polymorphisms and ischemic stroke in 6 study populations: association of lymphotoxin-alpha in nonhypertensive patients. Stroke 2009; 40:683695.