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

Abstract

The apolipoprotein A5 gene ( APOA5 ) is predominantly expressed in the liver and secreted into the blood where it resides on HDL and VLDL particles ( 1 ). Despite its very low levels in plasma, apoA5 appears to facilitate the interaction between circulating lipoprotein particles and proteoglycans on the vascular wall with the subsequent activation of proteoglycan-bound lipoprotein lipase ( 2-4 ). The APOA5 -1131T>C single nucleotide polymorphism (SNP) has been reported to be functional and is associated with reduced apoA5 concentration or activity ( 5 ). In particular, the APOA5 -1131C variant allele modulates the effects of dietary PUFA intake on fasting triglyceride levels, lipoprotein particle size ( 6 ), and obesity ( 7 ) and PUFA-APOA5 interactions are specifi c for dietary 6 PUFAs. The fatty acid composition of serum phospholipids mirrors dietary fatty acid intake over previous weeks and also refl ects Abstract We determined the contribution of the combination of FEN1 10154G>T with the most signifi cant association in the analysis of plasma arachidonic acid (AA, 20:4 6) and the APOA5 -1131T>C on phospholipid 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 signifi cant 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% confi dence 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). Signifi cant 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 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 signifi cant increase in CAD risk for this population subset despite their increased triglylcerides and decreased

Apolipoprotein A5 polymorphisms and risk of coronary artery disease: A meta-analysis

“…In a recent metaanalysis of the association of the APO A5 -1131T>C polymorphism and fasting blood lipids, Zhao et al found a strong association of the APO A5 -1131 T>C polymorphism with higher levels of TG (35). The -1131T>C polymorphism is located in the promoter polymorphism and risk of CAD were selected in this meta-analysis with 5,050 cases and 7,272 controls (11,12,14,16,17,(26)(27)(28)(29)(30)(31)(32)(33). For the S19W APOA5 gene polymorphisms, 5 studies were included in the metaanalysis with 2,196 cases and 3,933 controls (14,16,17,27,34).…”

Fatty Acids as Biocompounds: Their Role in Human Metabolism, Health and Disease - A Review. Part 2: Fatty Acid Physiological Roles and Applications in Human Health and Disease

“…Also, carriers of the rare allele of FADS SNP and their haplotypes had altered eicosanoid precursor levels and a lower prevalence of allergic disease and topical eczema 169 . Interactions have also been shown between the APOA5 and FEN1 polymorphisms and AA and n-6 PUFA levels in serum phospholipids and coronary artery disease 170 . Further, polymorphisms at the 5-LOX and COX-2 level have been shown to increase the risk of CHD and prostate cancer respectively, depending on DHA, EPA, LA and ALA intake.…”

Relationship between a Common Variant in the Fatty Acid Desaturase (FADS) Cluster and Eicosanoid Generation in Humans

“…FADS variation has also been associated with urinary excretion of 8-epi-prostaglandin F(2␣) in both controls and CAD patients, and this has been widely recognized as a sensitive and independent risk factor for CAD (25,26,43).…”