Highlights
- •2 PON1 genetic variants–smoking interactions impact coronary heart disease risk.
- •T allele of nonsynonymous rs662 variant is associated with higher risk in smokers.
- •Novel interaction of rs3735590 at miRNA binding site and smoking is identified.
- •CC homozygote of rs3735590 is associated with lower risk in never-smokers.
Abstract
Objective
Paraoxonase 1 (PON1) plays an important role in reducing the risk of coronary heart
disease (CHD). Smoking is known to reduce PON1 activity. We aimed to investigate the effects of interactions between PON1 variants and smoking on CHD in the Singaporean Chinese population.
Methods
In a case-control study nested within Singapore Chinese Health Study (N = 1914), subjects
with and without CHD were classified into never-smokers and ever-smokers (ever smoked
at least one cigarette a day for 1 year or longer). Associations at four independent
SNPs at the PON1 locus (rs3735590, rs3917550, rs662, rs3917481) with CHD were evaluated
using logistic regression, before/after stratification on smoking status. Interactions
between smoking and PON1 variants were analyzed with likelihood ratio tests, by including the SNP*smoking
interaction term in regression analyses.
Results
The T allele at the coding SNP, rs662, was associated with higher risk of CHD in ever-smokers
only (OR = 1.35, 95% CI 1.08–1.68; adjusted P = 0.036). At the miR-SNP, rs3735590,
carrying at least one copy of minor allele T was associated with increased risk of
CHD in a dominant manner in never-smokers only (OR = 1.53, 95% CI 1.11–2.11; adjusted
P = 0.036). Significant interactions between two PON1 SNPs and smoking in relation to CHD risk were identified (adjusted P = 0.012 for
rs662; adjusted P = 0.044 for rs3735590). These associations remained significant
after adjustment for known CHD risk factors and upon correction for multiple tests.
Conclusions
Two PON1 SNPs, rs662 and rs3735590, were found to significantly interact with cigarette smoking
to modulate the risk of CHD in the Singaporean Chinese population.
Keywords
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Article info
Publication history
Published online: February 24, 2015
Accepted:
January 19,
2015
Received in revised form:
January 17,
2015
Received:
September 11,
2014
Identification
Copyright
© 2015 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
