Interaction effects between Paraoxonase 1 variants and cigarette smoking on risk of coronary heart disease in a Singaporean Chinese population. Issue 1 (May 2015)

• Record Type: Journal Article
• Authors: Han, Yi; Dorajoo, Rajkumar; Ke, Tingjing; Ayala, Burger; Chang, Xuling; Khor, Chiea-Chuen; van Dam, Rob M.; Yuan, Jian-Min; Koh, Woon-Puay; Liu, Jianjun; Goh, Daniel Y.T.; Friedlander, Yechiel; Heng, Chew-Kiat
• Is Part Of: Atherosclerosis. Volume 240:Issue 1(2015)
• Page Start: 40
• Page End: 45
• Publication Date: 2015-05
• Subjects: Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2015.01.042
• Languages: English
• ISSNs: 0021-9150

Abstract

<abstract xml:lang="en" abstract-type="author" id="abs0010"> <title id="sectitle0010">Abstract</title> <sec> <title id="sectitle0015">Objective</title> <p id="abspara0010">Paraoxonase 1 (PON1) plays an important role in reducing the risk of coronary heart disease (CHD). Smoking is known to reduc<italic>e</italic> PON1 activity. We aimed to investigate the effects of interactions between <italic>PON1</italic> variants and smoking on CHD in the Singaporean Chinese population.</p> </sec> <sec> <title id="sectitle0020">Methods</title> <p id="abspara0015">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 <italic>PON1</italic> variants were analyzed with likelihood ratio tests, by including the SNP*smoking interaction term in regression analyses.</p> </sec> <sec> <title id="sectitle0025">Results</title> <p id="abspara0020">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 <italic>PON1</italic> 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.</p> </sec> <sec> <title id="sectitle0030">Conclusions</title> <p id="abspara0025">Two <italic>PON1</italic> SNPs, rs662 and rs3735590, were found to significantly interact with cigarette smoking to modulate the risk of CHD in the Singaporean Chinese population.</p> </sec> </abstract>