Interaction between peroxisome proliferator-activated receptor gamma and smoking on cardiovascular disease

• The first study to examine the combined effects of PPAR-γ and smoking on cardiovascular disease.
• Independent effects of PPAR-γ single nucleotide polymorphism and cardiovascular disease in a Chinese population

The aim of this study was to investigate the association between peroxisome proliferator-activator receptor-γ (PPAR-γ) genotype and additional gene–smoking interaction on cardiovascular disease (CVD) based on a Chinese population. A total of 1248 subjects (613 men, 635 women), with a mean age of 55.5 ± 11.8 years old, were selected, including 620 CVD patients and 628 normal controls. Logistic regression was performed to investigate association between single nucleotide polymorphism (SNP) and CVD. Generalized MDR (GMDR) was used to analysis the gene–environment interaction, cross-validation consistency, the testing balanced accuracy, and the sign test, to assess each selected interaction were calculated. The carriers of homozygous mutant of two SNP revealed increased CVD risk than those with wild-type homozygotes, OR (95% CI) were 1.31 (1.16–1.95) and 1.68 (1.29–2.06), respectively. GMDR analysis for one- to three-locus models indicated that there was a significant two-locus model (p = 0.0107) involving rs1805192 and smoking, indicating a potential gene–gene interaction between rs1805192 and smoking. Overall, the two- locus models had a cross-validation consistency of 10 of 10, and had the testing accuracy of 62.17%. We found that smokers with Pro/Ala or Ala/Ala genotype have highest CVD risk, compared to non-smokers with Pro/Pro genotype, OR (95% CI) was 3.46 (1.31–3.42), after covariates adjustment. We found a significant association between genotypes of variants in rs10865710 and rs1805192 with increased CVD risk and a potential gene–gene interaction between rs1805192 and smoking.