Abstract
Paraoxonase 1 gene (PON1) polymorphisms and dietary vegetable and fruit intake are both established determinants of ischemic stroke (IS). However, little is known about whether these factors jointly influence the risk of IS. We analyzed the main effects of PON1, as well as the interactions between PON1 and dietary vegetable or fruit intake with the risk of total IS and its subtypes in a family-based case-control study conducted among 2158 Chinese participants (1007 IS cases and 1151 IS-free controls) from 918 families. Conditional logistic regression models, with each family as a stratum, were used to examine the association between rs662 and IS. Gene-diet interactions were tested by including a cross-product term of dietary vegetable or fruit intake by rs662_G allele count in the models. Each copy of the PON1 rs662_G allele was associated with 28% higher risk of total IS (p = 0.008) and 32% higher risk of large artery atherosclerosis subtype (LAA) (p = 0.01). We observed an interaction between rs662 and vegetable intake for both total IS (p = 0.006) and LAA (p = 0.02) after adjustment for covariates. Individuals who carry the rs662_A allele may benefit to a greater extent from intake of vegetables and thus be more effectively protected from ischemic stroke, whereas carriers of the G allele may still remain at greater risk for ischemic stroke due to their genetic backgrounds even when they consume a high level of vegetables. More studies are needed to replicate our findings among other populations.
Highlights
Stroke is a major cause of death and disability worldwide [1,2,3]
Ischemic stroke can be classified into five subtypes according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria [7] based on their etiological mechanisms: large artery atherosclerosis (LAA), small arterial occlusion (SAO), cardio embolism (CE), stroke of other determined causes (OC), and stroke of undetermined causes (UND)
We found an interaction between Paraoxonase 1 gene (PON1) rs662 and vegetable intake for both total ischemic stroke (IS) (p = 0.001) and large artery atherosclerosis subtype (LAA) (p = 0.003) in our crude model (Table 3, Model 1)
Summary
Stroke is a major cause of death and disability worldwide [1,2,3]. According to the data from Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) [4], stroke ranks as the second leading cause of death after ischemic heart disease, and the third leading cause of Disability-Adjusted Life Years (DALYs) lost [5]. A meta-analysis including 7384 cases and 11,074 controls found that PON1 rs662_G was positively associated with risk of IS: the summary odds ratio (OR) (95% confidence interval (95% CI) was 1.10 (1.04–1.17) [18]. Another meta-analysis conducted among Caucasian, Japanese, and Chinese populations reported a significantly increased risk of IS for rs662_G carriers (OR: 1.21, 95% CI: 1.08–1.35, p = 0.0009) [19]
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