Genetic polymorphisms of 4 genes, methylenetetrahydrofolate reductase (MTHFR) and apolipoprotein E (ApoE) have been demonstrated to associate with the increased risk for both MDD and stroke, while the association between identified polymorphisms in angiotensin converting enzyme (ACE) and serum paraoxonase (PON1) with depression is still under debate, for the existing studies are insufficient in sample size.
Therefore, in this review we studied various researches, in which the association of PON1 SNPs with stroke had been investigated in different populations.
Ethnic differences in the association between PON1 variants with stroke could be due to the effects of PON1Val109Ile (overall P = 7.88 × 10(-3); AA P = 6.52 × 10(-4)), found at higher frequency in AA participants (1.16% vs. 0.02%) and whose protein is less stable than the common allele.
The aim was to assess the impact of epigenetic processes of human tumor necrosis factor (TNF-α) and paraoxonase (PON) promoters in the susceptibility to stroke when considering body composition and dietary intake.
The presence of rs705381 (-162) in the promoter region of PON1 was significantly associated with total stroke (P(adjusted) = 0.0007, OR = 0.57 [95% CI = 0.41-0.79]) and ischemic stroke (P(adjusted) = 0.0017, OR = 0.54 [95% CI = 0.37-0.79]) when analyzed using a dominant model, but was not associated with hemorrhagic stroke.
Extending previous PON1 genetic studies in stroke populations, our study emphasizes the PON1 activity as a potential anti-atherogenic element and proposes involvement of cholinesterase activities in its effects.
Future studies should investigate the interaction between additional polymorphisms within the PON1 gene and genetic variants in other folate metabolizing genes with folate intake on the risk of incident CHD and stroke.
A meta-analysis was therefore conducted by including the studies that examined the association between two common polymorphisms (L55M and Q192R) in the coding region of PON1 gene and the risk of stroke.
Because of the obvious publication bias, the association between paraoxonase 1 (PON-1) polymorphisms and stroke risk was not established although the OR of the meta-analysis suggested a positive result (OR = 1.14, 95% CI = 1.01-1.35).
Logistic regression analysis revealed PON1 activity ratio (odds ratio, OR=0.697, 95% CI, 0.541 to 0.898, P=0.005), PON1 192RR genotype (OR=3.434, 95% CI, 1.159 to 10.178, P=0.026) and PON1 status (PON1 activity ratio combined with PON1 192RR genotype; OR=1.406, 95% CI, 1.038 to 1.905, P=0.028) as significant predictors of stroke.
Logistic regression analysis revealed PON1 activity ratio (odds ratio, OR=0.697, 95% CI, 0.541 to 0.898, P=0.005), PON1 192RR genotype (OR=3.434, 95% CI, 1.159 to 10.178, P=0.026) and PON1 status (PON1 activity ratio combined with PON1 192RR genotype; OR=1.406, 95% CI, 1.038 to 1.905, P=0.028) as significant predictors of stroke.
Paraoxonase1 (PON1), Glutathione Reductase (GSH-Rd) and Malondialdehyde (MDA) levels were measured at day 1 and at day 5 following the onset of stroke.
The likely candidate genes associated with stroke are those that are associated with matrix deposition (stromelysin-1, MMP3), inflammation (IL-6), and lipid metabolism (hepatic lipase, APOE, PON1) and clotting (factor V Leiden, fibrinogen).