Abstract
We read with great interest the article by Alam and colleagues entitled “Synergistic Epistasis of Paraoxonase 1 (rs662 and rs85460) and Apolipoprotein E4 Genes in Pathogenesis of Alzheimer's Disease and Vascular Dementia” in which the investigators reported that a significant difference in the serum paraoxonase 1 (PON-1) activity was observed in patients with vascular dementia when compared to healthy controls, whereas there were no significant difference between Alzheimer’s disease and healthy controls. 1 However, we think that some points should be discussed.
Paraoxonase 1 hydrolyzes organophosphate substrate paraoxon and aromatic esters, such as phenylacetate, and has been shown to inhibit low-density lipoprotein oxidation. The authors stated that they defined inclusion and exclusion criteria as described in their previously published article. 2 In their previous study, they just defined cardiovascular diseases, diabetes, stroke, AIDS, and tuberculosis as exclusion criteria for selection of participants. Previous studies showed that certain diseases such as psoriasis, chronic renal failure, inflammatory bowel diseases, Parkinson’s disease, chronic liver disease, systemic lupus erythematosus, hyperlipidemia, and acute-phase response status could affect serum PON-1 activity in addition to stated diseases. 3,4 In this regard, simple laboratory tests such as erythrocyte sedimentation rate, C-reactive protein, routine biochemistry tests, and complete blood count could be achieved to exclude potential confounders. In addition, dietary supplements such as vitamin E, vitamin C, iron, zinc, and flavonoids can alter PON-1 activity. 5 Also, other contributing factors such as alcohol intake, smoking, and body mass index status have to be stated to provide meaningful data. 3
Another confounding factor for PON-1 activity assessment is medicine use. Lipid-lowering drugs, aspirin, fenofibrate, dexametazon, phenobarbital, and hormone replacement therapy, were shown to affect PON-1 activity. 6 Therefore, medicine use should be mentioned whether the participants use these kinds of drugs or not.
The authors found PON-1 activity levels as 4.3, 2.8, and 5.5 U/mL for Alzheimer’s disease, vascular dementia, and healthy control groups, respectively. However, almost all previous studies showed higher mean PON-1 activity levels. Xu et al described that PON-1 was distributed normally in the healthy population and its reference value ranged from 45.5 to 265.8 U/mL. 7 In this respect, the authors should reevaluate their results in terms of preanalytical, analytical, or postanalytical errors.
In conclusion, although this study contributes valuable information to the medical literature, clarifying these concerns will certainly provide a clearer picture when interpreting PON-1 activity among participants.