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

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.

Effects of paraoxonase 1 gene polymorphisms on heart diseases

“…Therefore, only 64 studies qualifying our strict selection criteria were involved in this meta-analysis. [ 3 , 8 – 70 ] We established a database of the extracted information from each eligible article (Table 1 ).…”

Paraoxonase (PON)-1: a brief overview on genetics, structure, polymorphisms and clinical relevance

“…Smoking is an important independent risk factor for CHD, and a study by Han et al 27 showed that cigarette smoking status together with the presence of common PON1 SNPs play a role in the risk of developing CHD. 27 In this case–control study nested within the Singapore Chinese Health Study, which was a prospective cohort of 63,257 participants recruited over 5 years, Han et al evaluated 1,914 Singaporean Chinese: 688 cases and 1,226 controls. The participants were stratified according to cigarette smoking status as ever-smokers (n=813), who answered yes to smoking at least one cigarette a day for a year or longer, and never-smokers (n=1,101).…”

“…The participants were stratified according to cigarette smoking status as ever-smokers (n=813), who answered yes to smoking at least one cigarette a day for a year or longer, and never-smokers (n=1,101). The T allele of the PON1 rs662 polymorphism was shown to be associated with an increased risk of CHD among ever-smokers only (odds ratio [OR]=1.35, 95% CI 1.08–1.68; adjusted p =0.036), whereas another PON1 SNP, rs3735590, was shown to be associated with an increase in CHD among never-smokers only (OR=1.53, 95% CI 1.11–2.11; adjusted p =0.036), 27 highlighting that more research is required on PON1 polymorphisms and CHD.…”

Analysis for interaction between interleukin-35 gene polymorphisms and risk factors on susceptibility to coronary heart disease in the Chinese Han population

“…The pathogenesis of coronary heart disease is very complex. It is not only affected by genetic factors and environmental factors independently, but also by the synergistic effect between them [24,25]. We were all known that alcohol drinking and smoking were two main modi ed risk factors for CHD [26,27].…”