FADS1
Acyl-CoA (8-3)-desaturase (EC 1.14.19.44) (Delta(5) fatty acid desaturase) (D5D) (Delta(5) desaturase) (Delta-5 desaturase) (Fatty acid desaturase 1) [FADSD5]
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Long-chain polyunsaturated fatty acids (LCPUFAs) are important constituents of biomembranes. Observation of blood fatty acids indicated that LCPUFA biosynthesis is affected by aging and FADS polymorphisms. This study examined the effects of aging and FADS polymorphisms on LCPUFA biosynthetic capacity via direct quantification using [U- C]linoleic acid. Healthy young (25-34 years) and elderly (65-74 years) participants were administered [U- C]linoleate, and its metabolites were monitored for 14 days. The time of maximum plasma concentration of C-arachidonic acid (ARA) was 4-5 days. The area under the curve of the C-ARA concentration differed by FADS1 rs174547 polymorphism (TT [100%] > TC [57%] > CC [37%]). Among C allele carriers, C-ARA formation was 32% lower in elderly than in young participants. This is the first report to directly demonstrate that LCPUFA biosynthetic capacity is regulated by FADS1 polymorphisms and decreased by aging in FADS1 C allele carriers.
MeSH Terms
- Adult
- Age Factors
- Aged
- Aging
- Alleles
- Arachidonic Acid
- Area Under Curve
- Fatty Acid Desaturases
- Fatty Acids, Unsaturated
- Female
- Healthy Volunteers
- Humans
- Linoleic Acid
- Male
- Polymorphism, Single Nucleotide
Keywords
- Aging
- Arachidonic acid
- Fatty acid conversion
- Linoleic acid
- Lipid metabolism
- Long-chain polyunsaturated fatty acid
To investigate genetic determinants of macular pigment optical density in women from the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women's Health Initiative Observational Study. 1585 of 2005 CAREDS participants had macular pigment optical density (MPOD) measured noninvasively using customized heterochromatic flicker photometry and blood samples genotyped for 440 single nucleotide polymorphisms (SNPs) in 26 candidate genes related to absorption, transport, binding, and cleavage of carotenoids directly, or via lipid transport. SNPs were individually tested for associations with MPOD using least-squares linear regression. Twenty-one SNPs from 11 genes were associated with MPOD (P ≤ 0.05) after adjusting for dietary intake of lutein and zeaxanthin. This includes variants in or near genes related to zeaxanthin binding in the macula (GSTP1), carotenoid cleavage (BCMO1), cholesterol transport or uptake (SCARB1, ABCA1, ABCG5, and LIPC), long-chain omega-3 fatty acid status (ELOVL2, FADS1, and FADS2), and various maculopathies (ALDH3A2 and RPE65). The strongest association was for rs11645428 near BCMO1 (βA = 0.029, P = 2.2 × 10(-4)). Conditional modeling within genes and further adjustment for other predictors of MPOD, including waist circumference, diabetes, and dietary intake of fiber, resulted in 13 SNPs from 10 genes maintaining independent association with MPOD. Variation in these single gene polymorphisms accounted for 5% of the variability in MPOD (P = 3.5 × 10(-11)). Our results support that MPOD is a multi-factorial phenotype associated with variation in genes related to carotenoid transport, uptake, and metabolism, independent of known dietary and health influences on MPOD.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Carotenoids
- Cross-Sectional Studies
- Female
- Humans
- Macular Degeneration
- Phenotype
- Polymorphism, Single Nucleotide
- Postmenopause
- Retinal Pigments
- Scavenger Receptors, Class B
- beta-Carotene 15,15'-Monooxygenase