Interaction effects between Paraoxonase 1 variants and cigarette smoking on risk of coronary heart disease in a Singaporean Chinese population

Yi Han, Rajkumar Dorajoo, Tingjing Ke, Burger Ayala, Xuling Chang, Chiea Chuen Khor, Rob M. van Dam, Jian Min Yuan, Woon Puay Koh, Jianjun Liu, Daniel Y.T. Goh, Yechiel Friedlander, Chew Kiat Heng*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Paraoxonase 1 (PON1) plays an important role in reducing the risk of coronary heart disease (CHD). Smoking is known to reduc. e 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.

Original languageEnglish
Pages (from-to)40-45
Number of pages6
JournalAtherosclerosis
Volume240
Issue number1
DOIs
StatePublished - 1 May 2015

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Ireland Ltd.

Keywords

  • Cigarette smoking
  • Coronary heart disease
  • Interaction
  • MiR-SNP
  • Paraoxonase 1
  • Singaporean Chinese
  • Single nucleotide polymorphism (SNP)

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