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

Clin Interv Aging. 2013;8:585-96. doi: 10.2147/CIA.S42096. Epub 2013 May 24.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Anthropometry
  • Biomarkers / blood
  • Blood Glucose / analysis
  • Chi-Square Distribution
  • Creatinine / urine
  • Delta-5 Fatty Acid Desaturase
  • Diet
  • Fatty Acid Desaturases / genetics*
  • Fatty Acids, Unsaturated / blood*
  • Genotype
  • Humans
  • Interleukin-6 / blood
  • Linear Models
  • Lipids / blood
  • Male
  • Middle Aged
  • Motor Activity
  • Oxidative Stress
  • Phospholipids / blood*
  • Polymorphism, Single Nucleotide*

Substances

  • Biomarkers
  • Blood Glucose
  • Delta-5 Fatty Acid Desaturase
  • Fatty Acids, Unsaturated
  • Interleukin-6
  • Lipids
  • Phospholipids
  • Creatinine
  • Fatty Acid Desaturases
  • FADS1 protein, human