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, 20:4ω6) 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.
Park
Ju Yeon
JY
National Research Laboratory of Clinical Nutrigenetics/Nutrigenomics, Department of Food and Nutrition, College of Human Ecology, Yonsei University, Seoul, Korea.
Paik
Jean Kyung
JK
Kim
Oh Yoen
OY
Chae
Jey Sook
JS
Jang
Yangsoo
Y
Lee
Jong Ho
JH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000235:genetics*; D001095:Arachidonic Acids / Q000097:blood; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D043371:Fatty Acids, Omega-6 / Q000378:metabolism*; D005260:Female; D045585:Flap Endonucleases / Q000235:genetics*; D006801:Humans; D008054:Lipid Peroxides / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D010743:Phospholipids / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D001095:Arachidonic Acids; D043371:Fatty Acids, Omega-6; D008054:Lipid Peroxides; D008077:Lipoproteins, LDL; D010743:Phospholipids; D014409:Tumor Necrosis Factor-alpha; D045585:Flap Endonucleases
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