Interaction effects between Paraoxonase 1 variants and cigarette smoking on risk of coronary heart disease in a 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.
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.
Yi
Y
Han
Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
Rajkumar
R
Dorajoo
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.
Tingjing
T
Ke
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.
Burger
B
Ayala
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.
Xuling
X
Chang
Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
Chiea-Chuen
CC
Khor
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
Rob M
RM
van Dam
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA; University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
Jian-Min
JM
Yuan
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore; Duke-NUS Graduate Medical School Singapore, Singapore.
Woon-Puay
WP
Koh
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.
Jianjun
J
Liu
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.
Daniel Y T
DY
Goh
School of Public Health and Community Medicine, Hebrew University of Jerusalem, Israel. Electronic address: yechielf@ekmd.huji.ac.il.
Yechiel
Y
Friedlander
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.
Chew-Kiat
CK
Heng
D000368:Aged; D043303:Aryldialkylphosphatase / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D003327:Coronary Disease / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors; D012846:Singapore / Q000453:epidemiology; D012907:Smoking / Q000009:adverse effects* / Q000208:ethnology
D043303:Aryldialkylphosphatase; C468406:PON1 protein, human
Cigarette smoking; Coronary heart disease; Interaction; Paraoxonase 1; Singaporean Chinese; Single nucleotide polymorphism (SNP); miR-SNP