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 F_2α (8-epi-PGF_2α) (P = 0.011) than rs174537GG. Changes in AA (P = 0.001), AA/DGLA (P = 0.017), EPA, DPA, EPA/ALA, and urinary 8-epi-PGF_2α (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-PGF_2α (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
• serum phospholipid polyunsaturated fatty acids
• oxidative stress markers
• nonobese men

Acknowledgements

This work was supported by the National Research Foundation, Ministry of Education, Science and Technology (Mid-career Researcher Program: 2012-0005604, M10642120002-06 N4212-00210, C00048, and 2012M3 A9C4048762), South Korea.

Disclosure

None of the authors had any personal or financial conflicts of interest.

Supplementary tables

Table S1 Information for the prescreening of eight single-nucleotide polymorphisms (SNPs) and selection of four SNPs

Table S2 Associations of FADS2 rs 2727270 genotypes with polyunsaturated fatty acid (PUFA) composition in serum phospholipids in men at baseline and 3-year follow-up

Table S3 Associations of FADS2 rs2727270 genotypes with LDL cholesterol, hs-CRP, cytokines, and oxidative stress markers in men at baseline and 3-year follow-up