Fatty acid desaturase (FADS) gene polymorphisms and insulin resistance in association with serum phospholipid polyunsaturated fatty acid composition in healthy Korean men: cross-sectional study

Background: We investigated the relationship between fatty acid desaturase (FADS) gene polymorphisms and insulin resistance (IR) in association with serum phospholipid polyunsaturated fatty acid (FA) composition in healthy Korean men. Methods: Healthy men (n = 576, 30 similar to 79 years old) were genotyped for rs174537 near FADS1 (FEN1-10154G>T), FADS2 (rs174575C>G, rs2727270C>T), and FADS3 (rs1000778C>T) SNPs. Dietary intake, serum phospholipid FA composition and HOMA-IR were measured. Results: Fasting insulin and HOMA-IR were significantly higher in the rs174575G allele carriers than the CC homozygotes, but lower in the rs2727270T allele carriers than the CC homozygotes. The proportion of linoleic acid (18:2 omega-6, LA) was higher in the minor allele carriers of FEN1-10154G>T, rs174575C>G and rs2727270C>T than the major homozygotes, respectively. On the other hand, the proportions of dihomo-gamma-linolenic acid (20:3 omega-6, DGLA) and arachidonic acid (20:4 omega-6, AA) in serum phospholipids were significantly lower in the minor allele carriers of FEN1-10154 G>T carriers and rs2727270C>T than the major homozygotes respectively. AA was also significantly lower in the rs1000778T allele carriers than the CC homozygotes. HOMA-IR positively correlated with LA and DGLA and negatively with AA/DGLA in total subjects. Interestingly, rs174575G allele carriers showed remarkably higher HOMA-IR than the CC homozygotes when subjects had higher proportions of DLGA (>= 1.412% in total serum phospholipid FA composition) (P for interaction = 0.009) or of AA (>= 4.573%) (P for interaction = 0.047). Conclusion: HOMA-IR is associated with FADS gene cluster as well as with FA composition in serum phospholipids. Additionally, HOMA-IR may be modulated by the interaction between rs174575C>G and the proportion of DGLA or AA in serum phospholipids.