Abstract
We determined the contribution of the combination of FEN1 10154G>T with the most significant association in the analysis of plasma arachidonic acid (AA, 20:4ω6) and the APOA5-1131T>C on phospholipid ω6PUFA and coronary artery disease (CAD). Patients with CAD (n = 807, 27-81 years of age) and healthy controls (n = 1123) were genotyped for FEN1 10154G>T and APOA5-1131T>C. We found a significant interaction between these two genes for CAD risk (P = 0.007) adjusted for confounding factors. APOA5-1131C allele carriers had a higher CAD risk [odds ratio (OR):1.484, 95% confidence interval (CI):1.31-1.96; P = 0.005] compared with APOA5-1131TT individuals in the FEN1 10154GG genotype group but not in the FEN1 10154T allele group (OR:1.096, 95%CI:0.84-1.43; P = 0.504). Significant interactions between these two genes were also observed for the AA proportion (P = 0.04) and the ratio of AA/linoleic acid (LA, 18:2ω6) (P = 0.004) in serum phospholipids of controls. The APOA5-1131C allele was associated with lower AA (P = 0.027) and AA/LA (P = 0.014) only in controls carrying the FEN1 10154T allele. In conclusion, the interaction between these genes suggests that the FEN1 10154T variant allele decreases AA and AA/LA in the serum phospholipids of carriers of the APOA5-1131C allele, but contributes no significant increase in CAD risk for this population subset despite their increased triglylcerides and decreased apoA5.
Highlights
We determined the contribution of the combination of FEN1 10154G>T with the most significant association in the analysis of plasma arachidonic acid (AA, 20:46) and the apolipoprotein A5 gene (APOA5)-1131T>C on phospholipid 6PUFA and coronary artery disease (CAD)
We found an interaction between APOA5 -1131T>C and FEN1 10154G>T for CAD risk
The interaction effect between these two genes revealed that carriers of the APOA5 -1131C allele, despite their increased triglycerides and decreased apoA5, were not associated with CAD risk when carrying the FEN1 10154T variant allele as compared with participants homozygous for the APOA5 -1131T allele
Summary
We determined the contribution of the combination of FEN1 10154G>T with the most significant association in the analysis of plasma arachidonic acid (AA, 20:46) and the APOA5-1131T>C on phospholipid 6PUFA and coronary artery disease (CAD). APOA5-1131C allele carriers had a higher CAD risk [odds ratio (OR):1.484, 95% confidence interval (CI):1.31–1.96; P = 0.005] compared with APOA5-1131TT individuals in the FEN1 10154GG genotype group but not in the FEN1 10154T allele group (OR:1.096, 95%CI:0.84–1.43; P = 0.504) Significant interactions between these two genes were observed for the AA proportion (P = 0.04) and the ratio of AA/ linoleic acid (LA, 18:26) (P = 0.004) in serum phospholipids of controls. Our aim was to determine the contribution of the combination of the FEN1 10154G>T and APOA5 -1131T>C SNPs on serum phospholipid 6 PUFA metabolism and CAD
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