Effect of SYTL3-SLC22A3 Variants, Their Haplotypes, and G × E Interactions on Serum Lipid Levels and the Risk of Coronary Artery Disease and Ischaemic Stroke

Figures

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  Figure 1. The interactions of the SLC22A3 rs539298 SNP and diabetes, drinking, hypertension, smoking, age, sex, and BMI on the risk of CAD and IS. The rs539298AG/GG genotypes interacted with alcohol consumption to decrease the risk of CAD (A) (OR = 0.53, 95% CI = 0.37–0.77) and IS (B) (OR = 0.44, 95% CI = 0.30–0.65). *P < 0.01.

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  Figure 2. The linkage disequilibrium (LD) represents pair wise D' × 100 in the CAD (A) and IS (B) groups.

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  Figure 3. The interactions between the SYTL3-SLC22A3 haplotypes and the risk of CAD and IS. CAD, coronary artery disease; IS, ischaemic stroke. (A) The SYTL3-SLC22A3 A-C-A-A-A-A haplotype interacted with age > 75 and smoking to increase the risk of CAD. (B) The interaction between the SYTL3-SLC22A3 A-C-A-A-C-G haplotype and alcohol consumption decreased the risk of CAD. (C) The interactions between SYTL3-SLC22A3 G-T-C-G-C-A and cigarette smoking and BMI ≥ 24 kg/m2 increased the risk of CAD. (D) The SYTL3-SLC22A3 A-T-A-A-C-A haplotype interacted with age > 75 and smoking to increase the risk of CAD. (E) The interactions between the SYTL3-SLC22A3 A-C-A-A-A-G haplotype and female and alcohol consumption decreased the risk of IS. (F) The SYTL3-SLC22A3 A-C-A-A-A-A haplotype interacted with hypertension and smoking to increase the risk of IS. (G) The interactions between the SYTL3-SLC22A3 A-C-A-A-C-G haplotype and hypertension increased the risk of IS, and alcohol consumption decreased the risk of IS. (H) The interactions between the SYTL3-SLC22A3 A-T-A-A-C-A haplotype and age > 75 and smoking increased the risk of IS. *P < 0.05 and **P < 0.01.

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  Figure 4. The association between the genotypes of six SYTL3-SLC22A3 SNPs and blood lipid levels in the control group. HDL-C, high-density lipoprotein cholesterol; TC, total cholesterol; ApoA1, apolipoprotein A1; TG, triglyceride; ApoB, apolipoprotein B; LDL-C, low-density lipoprotein cholesterol; ApoA1/ApoB, the ratio of apolipoprotein A1 to apolipoprotein B. A *P < 0.008 (after adjusting for 6 independent tests by the Bonferroni correction) was considered statistically significant. (A), rs9364496; (B), rs6455600; (C), rs2129209; (D), rs9456350; (E), rs446809; and (F), rs539298 SNPs.

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  Figure 5. The interactions of the SYTL3-SLC22A3 SNPs and drinking, BMI and smoking on serum lipid levels. TC, total cholesterol; TG, triglyceride; BMI, body mass index; ApoA1, apolipoprotein A1; HDL-C, high-density lipoprotein cholesterol. A P ≤ 0.00125 (corresponding to P < 0.05 after adjusting for five environmental exposures multiplied by eight outcomes by the Bonferroni correction) was considered statistically significant. (A), rs9364496-BMI on TC; (B), rs9364496-smoking on TG; (C), rs6455600-BMI on TG; (D), rs6455600-smoking on TG; (E), rs2129209-BMI on TC; (F), rs2129209-drinking on HDL-C; (G), rs9456350-BMI on TG; (H), rs9456350-drinking on HDL-C; (I), rs446809-drinking on HDL-C; (J), rs539298-drinking on ApoA1; (K), rs539298-drinking on HDL-C; (L), rs539298-BMI on TC.

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  Figure 6. Association between environmental exposures as well as the candidate loci and serum lipid parameters in CAD (A) or IS (B). CAD, coronary artery disease; IS, ischaemic stroke. SBP, systolic blood pressure; TC, total cholesterol; BMI, body mass index; TG, triglyceride; ApoA1/B, the ratio of apolipoprotein A1 to apolipoprotein B; HDL-C, high-density lipoprotein cholesterol; DBP, diastolic blood pressure; LDL-C, low-density lipoprotein cholesterol; ApoA1, apolipoprotein A1; PP, pulse pressure; ApoB, apolipoprotein B; Glu, glucose.