Interactions between the APOA5-1131T>C and the FEN1 10154G>T polymorphisms on ω6 polyunsaturated fatty acids in serum phospholipids and coronary artery disease

We determined the contribution of the combination of FEN1 10154G>T with the most significant association in the analysis of plasma arachidonic acid (AA, 20:4 omega 6) and the APOA5-1131T>C on phospholipid omega 6PUFA 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, 18:2 omega 6) (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.-Park, J. Y., J. K. Paik, O. Y. Kim, J. S. Chae, Y. Jang, and J. H. Lee. Interactions between the APOA5-1131T>C and the FEN1 10154G>T polymorphisms on omega 6 polyunsaturated fatty acids in serum phospholipids and coronary artery disease. J. Lipid Res. 2010. 51: 3281-3288.