Yi Han1, Rajkumar Dorajoo2, Tingjing Ke1, Burger Ayala3, Xuling Chang1, Chiea-Chuen Khor2, Rob M van Dam4, Jian-Min Yuan5, Woon-Puay Koh6, Jianjun Liu7, Daniel Y T Goh1, Yechiel Friedlander8, Chew-Kiat Heng9. 1. Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Khoo Teck Puat - National University Children's Medical Institute, National University Health System, Singapore. 2. Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore. 3. Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Khoo Teck Puat - National University Children's Medical Institute, National University Health System, Singapore; School of Public Health and Community Medicine, Hebrew University of Jerusalem, Israel. 4. Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore. 5. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA; University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA. 6. Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore; Duke-NUS Graduate Medical School Singapore, Singapore. 7. Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore. 8. School of Public Health and Community Medicine, Hebrew University of Jerusalem, Israel. Electronic address: yechielf@ekmd.huji.ac.il. 9. Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Khoo Teck Puat - National University Children's Medical Institute, National University Health System, Singapore. Electronic address: paehck@nus.edu.sg.
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.
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.
Authors: S M Herrmann; H Blanc; O Poirier; D Arveiler; G Luc; A Evans; P Marques-Vidal; J M Bard; F Cambien Journal: Atherosclerosis Date: 1996-10-25 Impact factor: 5.162
Authors: M Navab; S Hama-Levy; B J Van Lenten; G C Fonarow; C J Cardinez; L W Castellani; M L Brennan; A J Lusis; A M Fogelman; B N La Du Journal: J Clin Invest Date: 1997-04-15 Impact factor: 14.808
Authors: Yazmín Hernández-Díaz; Carlos Alfonso Tovilla-Zárate; Isela Esther Juárez-Rojop; Thelma Beatriz González-Castro; Candelario Rodríguez-Pérez; María Lilia López-Narváez; José Manuel Rodríguez-Pérez; José Francisco Cámara-Álvarez Journal: Medicine (Baltimore) Date: 2016-11 Impact factor: 1.889