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Genetic variants of the FADS gene cluster are associated with erythrocyte membrane LC PUFA levels in patients with mild cognitive impairment

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The journal of nutrition, health & aging

Abstract

Background

Long-chain (> 20 C-atoms) polyunsaturated fatty acids (LC PUFAs) of both the omega-6 (n-6) and omega-3 (n-3) series are important for the functional integrity of brain and thereby cognition, memory and mood. Clinical studies observed associations between altered LC PUFA levels and neurodegenerative diseases such as Alzheimer´s disease and its prodromal stage, mild cognitive impairment (MCI).

Methods

The present study examined the LC PUFA status of MCI patients with specific view on the relative LC n-3 PUFA levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in erythrocyte membranes (omega-3 index). 12 single nucleotide polymorphisms (SNPs) of the FADS1, FADS2, and FADS3 gene clusters were genotyped in 111 MCI patients and evaluated associations with PUFA levels in erythrocyte membranes (primary outcome). In addition, the associations between FADS SNPs and LC PUFA levels with serum lipid levels as well as depressive symptoms were examined (secondary outcomes).

Results

Minor allele carrier of rs174546, rs174548 (FADS1), rs3834458, rs1535, rs174574, rs174575, rs174576, and rs174578 (FADS2) showed significant higher n-6 and n-3 precursor PUFA levels (linoleic acid, and alpha-linolenic acid, respectively) and lower arachidonic acid (AA) levels in erythrocyte membranes compared to the major allele carriers. Differences in EPA and DHA levels were not significant. Minor allele carriers of rs174574, rs174576 and rs174578 (FADS2) and rs174455 (FADS3) exhibited significant higher triglyceride levels, whereas minor allele carriers for rs174449 and rs174455 (FADS3) exhibited significant higher total- and LDL-cholesterol levels compared to the more common variant. The mean omega-3 index of the study cohort was 6.19 ± 1.55 %. In more than 85 % of the patients, the omega-3 index was below 8 % and in 23 % below 5 %. Moreover, it was shown that a low DHA status and omega-3 index was associated with depressive symptoms (Beck’s depression-inventory).

Discussion and conclusion

These findings indicate an association between several FADS genotypes for higher n-6 and n-3 precursor PUFA and lower AA levels in erythrocyte membranes in minor compared to major allele carriers. To what extent FADS genotypes and a lower conversion of LA and ALA to biologically important LC PUFAs such as AA, EPA and DHA contributes to cognitive decline should be investigated in further trials. Nevertheless, the omega-3 index in this cohort of MCI patients can be classified as insufficient.

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Authors and Affiliations

  1. Institute of Food Science and Human Nutrition, Leibniz University Hannover, Hanover, Germany

    Jan Philipp Schuchardt, J. Willers, A. Gingrich & A. Hahn

  2. Department of Neurology, Charité - University Medicine Berlin, Berlin, Germany

    T. Köbe, V. Witte & A. Flöel

  3. NeuroCure Cluster of Excellence, Charité - University Medicine Berlin, Berlin, Germany

    V. Witte & A. Flöel

  4. Max Planck Institute of Human Cognitive and Brain Sciences, Department of Neurology, Leipzig, Germany and SFB 1052 Obesity Mechanism subproject A1, University of Leipzig, Leipzig, Germany

    V. Witte

  5. Institute of General Practice, Goethe-University, Frankfurt am Main, Germany

    V. Tesky & J. Pantel

  6. Department of Psychiatry, Psychotherapy and Psychosomatic, University Medicine, Halle/Saale, Germany

    D. Rujescu

  7. Hannover Unified Biobank, Hannover Medical School, Hannover, Germany

    T. Illig

  8. Institute of Human Genetics, Hannover Medical School, Hannover, Germany

    T. Illig

  9. Center for Stroke Research Berlin, Charité - University Medicine Berlin, Berlin, Germany

    A. Flöel

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  1. Jan Philipp Schuchardt
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Schuchardt, J.P., Köbe, T., Witte, V. et al. Genetic variants of the FADS gene cluster are associated with erythrocyte membrane LC PUFA levels in patients with mild cognitive impairment. J Nutr Health Aging 20, 611–620 (2016). https://doi.org/10.1007/s12603-016-0720-3

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  • DOI: https://doi.org/10.1007/s12603-016-0720-3

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