Association of polymorphisms in FADS gene with age-related changes in serum phospholipid polyunsaturated fatty acids and oxidative stress markers in middle-aged nonobese men

Abstract

Background: To investigate the association of FADS gene polymorphisms with age-related changes in polyunsaturated fatty acids (PUFAs) in serum phospholipids and oxidative stress markers.

Methods: We genotyped 122 nonobese men aged 35-59 years without any known diseases at baseline for rs174537 near FADS1 (FEN1 rs174537G > T), FADS2 (rs174575, rs2727270), and FADS3 (rs1000778), and followed them for 3 years.

Results: Among the four single-nucleotide polymorphisms, the minor variants of rs174537 and rs2727270 were significantly associated with lower concentrations of long-chain PUFAs. However, rs174537G > T showed stronger association. At baseline, men with the rs174537T allele had lower arachidonic acid (AA) and AA/linoleic acid (LA), and higher interleukin (IL)-6 levels than rs174537GG counterparts. After 3 years, rs174537GG men had significantly increased AA (P = 0.022), AA/dihomo-γ-linolenic acid (DGLA) (P = 0.007), docosapentaenoic acid (DPA), low-density lipoprotein (LDL) cholesterol, and oxidized LDL (ox-LDL), but decreased eicosatrienoic acid. The rs174537T group showed significantly increased γ-linolenic acid and ox-LDL, and decreased eicosadienoic acid, eicosapentaenoic acid (EPA)/α-linolenic acid (ALA), and IL-6. After 3 years, the rs174537T group had lower AA (P < 0.001), AA/DGLA (P = 0.019), EPA, DPA, EPA/ALA, and urinary 8-epi-prostaglandin F2α (8-epi-PGF2α) (P = 0.011) than rs174537GG. Changes in AA (P = 0.001), AA/DGLA (P = 0.017), EPA, DPA, EPA/ALA, and urinary 8-epi-PGF2α (P < 0.001) were significantly different between the groups after adjusting for baseline values. Overall, changes in AA positively correlated with changes in urinary 8-epi-PGF2α (r = 0.249, P = 0.007), plasma ox-LDL (r = 0.199, P = 0.045), and serum IL-6 (r = 0.289, P = 0.004).

Conclusion: Our data show that FADS polymorphisms can affect age-associated changes in serum phospholipid long-chain PUFAs, Δ5-desaturase activity, and oxidative stress in middle-aged nonobese men. In particular, the rs174537T allele did not show the age-associated increases in AA and Δ5-desaturase activity seen with the rs174537GG genotype.

Keywords: FADS gene; age-related changes; nonobese men; oxidative stress markers; serum phospholipid polyunsaturated fatty acids.

Figure 1

Serum phospholipid AA (20:4 ω6), the ratio of 20:4 ω6/20:3 ω6, and urinary levels of 8-epi-PGF_2α according to FEN1 rs174537 G > T in men at baseline (□) and 3-year follow-up (▪). Notes:^†P < 0.05; ^††P < 0.01 for baseline vs 3 years, tested by paired t-test; ^‡P < 0.05; ^‡‡P < 0.01; and ^‡‡‡P < 0.001 for GG vs T-allele group, tested by independent t-test; *after adjusting for baseline values. Changes are differences between baseline and 3 years; values are means ± standard error. Abbreviation: 8-epi-PGF_2α, urinary 8-epi-prostaglandin F_2α.

Figure 2

Relation of changes in serum phospholipid arachidonic acid with changes in oxidized LDL, urinary 8-epi-PGF_2α and serum IL-6 in all male subjects. Note: Changes are differences between baseline and 3 years. Abbreviations: 8-epi-PGF_2α, urinary 8-epi-prostaglandin F_2α; LDL, low-density lipoprotein; IL, interleukin.