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Identification of Novel Genetic Determinants of Erythrocyte Membrane Fatty Acid Composition among Greenlanders.

ABSTRACT: Fatty acids (FAs) are involved in cellular processes important for normal body function, and perturbation of FA balance has been linked to metabolic disturbances, including type 2 diabetes. An individual's level of FAs is affected by diet, lifestyle, and genetic variation. We aimed to improve the understanding of the mechanisms and pathways involved in regulation of FA tissue levels, by identifying genetic loci associated with inter-individual differences in erythrocyte membrane FA levels. We assessed the levels of 22 FAs in the phospholipid fraction of erythrocyte membranes from 2,626 Greenlanders in relation to single nucleotide polymorphisms genotyped on the MetaboChip or imputed. We identified six independent association signals. Novel loci were identified on chromosomes 5 and 11 showing strongest association with oleic acid (rs76430747 in ACSL6, beta (SE): -0.386% (0.034), p = 1.8x10-28) and docosahexaenoic acid (rs6035106 in DTD1, 0.137% (0.025), p = 6.4x10-8), respectively. For a missense variant (rs80356779) in CPT1A, we identified a number of novel FA associations, the strongest with 11-eicosenoic acid (0.473% (0.035), p = 2.6x10-38), and for variants in FADS2 (rs174570), LPCAT3 (rs2110073), and CERS4 (rs11881630) we replicated known FA associations. Moreover, we observed metabolic implications of the ACSL6 (rs76430747) and CPT1A (rs80356779) variants, which both were associated with altered HbA1c (0.051% (0.013), p = 5.6x10-6 and -0.034% (0.016), p = 3.1x10-4, respectively). The latter variant was also associated with reduced insulin resistance (HOMA-IR, -0.193 (0.050), p = 3.8x10-6), as well as measures of smaller body size, including weight (-2.676 kg (0.523), p = 2.4x10-7), lean mass (-1.200 kg (0.271), p = 1.7x10-6), height (-0.966 cm (0.230), p = 2.0x10-5), and BMI (-0.638 kg/m2 (0.181), p = 2.8x10-4). In conclusion, we have identified novel genetic determinants of FA composition in phospholipids in erythrocyte membranes, and have shown examples of links between genetic variants associated with altered FA membrane levels and changes in metabolic traits.

SUBMITTER: Andersen MK

PROVIDER: S-EPMC4920407 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Identification of Novel Genetic Determinants of Erythrocyte Membrane Fatty Acid Composition among Greenlanders.

Andersen Mette Korre MK Jørsboe Emil E Sandholt Camilla Helene CH Grarup Niels N Jørgensen Marit Eika ME Færgeman Nils Joakim NJ Bjerregaard Peter P Pedersen Oluf O Moltke Ida I Hansen Torben T Albrechtsen Anders A

PLoS genetics 20160624 6

Fatty acids (FAs) are involved in cellular processes important for normal body function, and perturbation of FA balance has been linked to metabolic disturbances, including type 2 diabetes. An individual's level of FAs is affected by diet, lifestyle, and genetic variation. We aimed to improve the understanding of the mechanisms and pathways involved in regulation of FA tissue levels, by identifying genetic loci associated with inter-individual differences in erythrocyte membrane FA levels. We as ...[more]

PMID: 27341449

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Project description:BackgroundDietary fatty acids have been shown to be associated with the development of cognition. However, research on the role of fatty acid intake in dietary patterns and fatty acid patterns (FAPs) in the development of cognitive function is limited. The aim of this study was to explore the correlation between dietary patterns and FAPs and to provide available evidence for preventing mild cognitive impairment (MCI) through these patterns.Materials and methodsThe 973 participants aged between 65 and 85 were recruited from 2020 to 2021 for this multicenter research in Beijing. Neuropsychological tests were used for cognitive evaluation, and data of dietary intake in the past 12 months were collected with semi-quantitative food frequency questionnaire. The erythrocyte membrane fatty acid profile was tested by chromatography and mass spectrometry lipid profiling. Factor analysis was used to derive the main dietary patterns and FAPs. Pearson's correlation or Spearman's correlation was used to explore the association between dietary patterns and FAPs. Binary logistic regression was applied to examine the relationship between patterns and cognitive function.ResultsSix dietary patterns and six FAPs were identified, explaining 53.4 and 80.9% of the total variance separately. After adjusting all potential confounders, T3 of the pattern 1 and FAP2 were the independent protect factors for MCI, respectively (OR 0.601, 95% CI [0.395, 0.914]; OR 0.108, 95% CI [0.019, 0.623]). Rich of SM (26:0), SM (24:1), and SM (26:1) is the characteristic of FAP2. A positive correlation was found between component scores of dietary pattern1 and FAP2 (r = 0.441, p = 0.001). People who adhered to a reasonable intake of animal flesh consumed more various long-chain fatty acids as well.ConclusionThe erythrocyte membrane metabolites, SM (26:0), SM (24:1), and SM (26:1), might function as early biomarkers for predicting or monitoring of cognitive aging in the elderly. The dietary pattern with recommended animal flesh consumption was significantly associated with FAP characterized by very long-chain SMs. This dietary pattern affected FAP, which might achieve the ultimate goal of neuroprotection through the very long-chain SMs. A rational intake of dietary fatty acids might be an effective way on preventing MCI in the elderly.

Dataset Information

Identification of Novel Genetic Determinants of Erythrocyte Membrane Fatty Acid Composition among Greenlanders.

Publications

Identification of Novel Genetic Determinants of Erythrocyte Membrane Fatty Acid Composition among Greenlanders.

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