I:10.1371/Epigenetics journal.pone.0055869.t1,6.15(4.50, 7.93) 0.2260.07 0.03(0.02, 0.04) 1.6560.39 0.08(0.06, 0.10)5.28(3.51, 7.70) 0.2660.10 0.04(0.03, 0.05) 1.8460.43 0.08(0.06, 0.09)0.699 ,0.001 ,0.001 ,0.001 0.Table 4. Risk estimate based on the distributions of genotype and allele frequency.SNP rs174537G/Tgenotype GG GT TTControl (n = 510) 124 246 140 236 224 50 500 10 323 157 30 211 241CAD (n = 505) 154 256 95 224 237 44 501 4 284 171 50 208 245Allele OR(95 CI), value1 0.743(0.624, 0.884), 0.Additive OR(95 CI), P value2 reference 0.837(0.623, 1.124), 0.236 0.548(0.385, 0.780), 0.Dominant 25033180 OR(95 CI), P value2 reference 0.732(0.555, 0.967), 0.rs174616C/TCC TC TT1.019(0.846, 1.228), 0.reference 1.097(0.846, 1.422), 0.485 0.916(0.587, 1.430), 0.reference 1.064 (0.830, 1.364), 0.rs174611C/TTT CT0.402(0.126, 1.285), 0.reference 0.376 (0.117, 1.210), 0.reference 0.376 (0.117, 1.210), 0.101 reference 1.329(1.033, 1.711), 0.rs174460C/TTT TC CC1.357(1.106, 1.665), 0.reference 1.221(0.932, 1.600), 0.147 1.896(1.172, 3.067), 0.rs174450A/CAA AC CC0.981(0.817, 1.177), 0.reference 1.023(0.787, 1.330), 0.865 0.904(0.592, 1.380), 0.reference 1.000(0.778, 1.286), 0.1: P values derived from the chi-square test of allele frequency. 2: P values derived from logistic regression after adjustment for gender and age of genotype distribution. doi:10.1371/journal.pone.0055869.tFADS Gene, Desaturase Activity and CADFigure 1. The schematic overview of linkage disequilibrium of the five studied SNPs (located on chromosome 11). Color scheme represent D9/LOD, while the numbers stand for r2. doi:10.1371/journal.pone.0055869.gof rs174537 G.T and rs174460 C.T were different between the CAD and control group after adjustment. For the rs174537 SNP, T allele carrier of controls had a lower level of D9D-18. While G allele carrier of CAD patients showed increased D6D, D9D-16, D9D-18, and decreased D5D. Our data demonstrated that the rs174537 T allele was associated with a lower risk of CAD [OR 0.743, 95 CI (0.624, 0.884), p = 0.001]. This result is Epigenetic Reader Domain consistent with the report of Jung Hyun in Korea [22]. And a possible protective effect of increased D5D activity on coronary heart disease may partly be mediated by increased plasma level of DHA. Rs174537 is located in an intron and is adjacent to 
the FADS1 gene. Recently, several studies have reported that rs174537 is in linkage disequilibrium with rs174546 (r2 = 0.99) and 1326631 is associated with expression of FADS1 in lymphoblastoid cells [23]. Therefore, this variant may be a marker of other functional polymorphisms or in linkage with other variants affecting fatty acid concentrations and, consequently, CAD. For the rs174460 SNP, C allele carriers, including controls and patients, had higher levels of D6D, D9D-16, D9D-18, and lower level of D5D. Our findings suggest that the rs174460 C allele was associated with a higher risk of CAD [OR 1.357, 95 CI (1.106, 1.665), p = 0.003]. Rs174460 is located in the FADS3 gene. The FADS3 gene function is still unknown; however, it is presumed to have desaturase activity because of its sequence homology with FADS1 and FADS2 genes (62 and 70 nucleotide sequence identity,Table 5. Effects of rs174537 SNP on lipids and plasma fatty acid levels.CharacteristicsControls GG(n = 
124) GT+TT(n = 386) 4.32(3.74, 4.77) 1.02(0.77, 1.34) 1.25(1.04, 1.48)g 2.5760.63g 4.93(4.57, 5.43) 22.2863.76 0.66(0.45, 0.92) 9.0262.01 14.7063.27 36.64(32.81, 40.13)g 0.16(0.00, 0.43) 0.44(0.29, 0.68) 1.29(0.97, 1.69) 7.8662.4.I:10.1371/journal.pone.0055869.t1,6.15(4.50, 7.93) 0.2260.07 0.03(0.02, 0.04) 1.6560.39 0.08(0.06, 0.10)5.28(3.51, 7.70) 0.2660.10 0.04(0.03, 0.05) 1.8460.43 0.08(0.06, 0.09)0.699 ,0.001 ,0.001 ,0.001 0.Table 4. Risk estimate based on the distributions of genotype and allele frequency.SNP rs174537G/Tgenotype GG GT TTControl (n = 510) 124 246 140 236 224 50 500 10 323 157 30 211 241CAD (n = 505) 154 256 95 224 237 44 501 4 284 171 50 208 245Allele OR(95 CI), value1 0.743(0.624, 0.884), 0.Additive OR(95 CI), P value2 reference 0.837(0.623, 1.124), 0.236 0.548(0.385, 0.780), 0.Dominant 25033180 OR(95 CI), P value2 reference 0.732(0.555, 0.967), 0.rs174616C/TCC TC TT1.019(0.846, 1.228), 0.reference 1.097(0.846, 1.422), 0.485 0.916(0.587, 1.430), 0.reference 1.064 (0.830, 1.364), 0.rs174611C/TTT CT0.402(0.126, 1.285), 0.reference 0.376 (0.117, 1.210), 0.reference 0.376 (0.117, 1.210), 0.101 reference 1.329(1.033, 1.711), 0.rs174460C/TTT TC CC1.357(1.106, 1.665), 0.reference 1.221(0.932, 1.600), 0.147 1.896(1.172, 3.067), 0.rs174450A/CAA AC CC0.981(0.817, 1.177), 0.reference 1.023(0.787, 1.330), 0.865 0.904(0.592, 1.380), 0.reference 1.000(0.778, 1.286), 0.1: P values derived from the chi-square test of allele frequency. 2: P values derived from logistic regression after adjustment for gender and age of genotype distribution. doi:10.1371/journal.pone.0055869.tFADS Gene, Desaturase Activity and CADFigure 1. The schematic overview of linkage disequilibrium of the five studied SNPs (located on chromosome 11). Color scheme represent D9/LOD, while the numbers stand for r2. doi:10.1371/journal.pone.0055869.gof rs174537 G.T and rs174460 C.T were different between the CAD and control group after adjustment. For the rs174537 SNP, T allele carrier of controls had a lower level of D9D-18. While G allele carrier of CAD patients showed increased D6D, D9D-16, D9D-18, and decreased D5D. Our data demonstrated that the rs174537 T allele was associated with a lower risk of CAD [OR 0.743, 95 CI (0.624, 0.884), p = 0.001]. This result is consistent with the report of Jung Hyun in Korea [22]. And a possible protective effect of increased D5D activity on coronary heart disease may partly be mediated by increased plasma level of DHA. Rs174537 is located in an intron and is adjacent to the FADS1 gene. Recently, several studies have reported that rs174537 is in linkage disequilibrium with rs174546 (r2 = 0.99) and 1326631 is associated with expression of FADS1 in lymphoblastoid cells [23]. Therefore, this variant may be a marker of other functional polymorphisms or in linkage with other variants affecting fatty acid concentrations and, consequently, CAD. For the rs174460 SNP, C allele carriers, including controls and patients, had higher levels of D6D, D9D-16, D9D-18, and lower level of D5D. Our findings suggest that the rs174460 C allele was associated with a higher risk of CAD [OR 1.357, 95 CI (1.106, 1.665), p = 0.003]. Rs174460 is located in the FADS3 gene. The FADS3 gene function is still unknown; however, it is presumed to have desaturase activity because of its sequence homology with FADS1 and FADS2 genes (62 and 70 nucleotide sequence identity,Table 5. Effects of rs174537 SNP on lipids and plasma fatty acid levels.CharacteristicsControls GG(n = 124) GT+TT(n = 386) 4.32(3.74, 4.77) 1.02(0.77, 1.34) 1.25(1.04, 1.48)g 2.5760.63g 4.93(4.57, 5.43) 22.2863.76 0.66(0.45, 0.92) 9.0262.01 14.7063.27 36.64(32.81, 40.13)g 0.16(0.00, 0.43) 0.44(0.29, 0.68) 1.29(0.97, 1.69) 7.8662.4.
