Identification of Novel Genetic Determinants of Erythrocyte Membrane Fatty Acid Composition among Greenlanders
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 un...
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Online Access: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4920407/ http://www.ncbi.nlm.nih.gov/pubmed/27341449 https://doi.org/10.1371/journal.pgen.1006119 |
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ftpubmed:oai:pubmedcentral.nih.gov:4920407 2023-05-15T16:30:58+02:00 Identification of Novel Genetic Determinants of Erythrocyte Membrane Fatty Acid Composition among Greenlanders Andersen, Mette Korre Jørsboe, Emil Sandholt, Camilla Helene Grarup, Niels Jørgensen, Marit Eika Færgeman, Nils Joakim Bjerregaard, Peter Pedersen, Oluf Moltke, Ida Hansen, Torben Albrechtsen, Anders 2016-06-24 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4920407/ http://www.ncbi.nlm.nih.gov/pubmed/27341449 https://doi.org/10.1371/journal.pgen.1006119 en eng Public Library of Science http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4920407/ http://www.ncbi.nlm.nih.gov/pubmed/27341449 http://dx.doi.org/10.1371/journal.pgen.1006119 © 2016 Andersen et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. CC-BY Research Article Text 2016 ftpubmed https://doi.org/10.1371/journal.pgen.1006119 2016-07-24T00:04:26Z 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 ... Text greenlander* PubMed Central (PMC) PLOS Genetics 12 6 e1006119 |
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Research Article Andersen, Mette Korre Jørsboe, Emil Sandholt, Camilla Helene Grarup, Niels Jørgensen, Marit Eika Færgeman, Nils Joakim Bjerregaard, Peter Pedersen, Oluf Moltke, Ida Hansen, Torben Albrechtsen, Anders Identification of Novel Genetic Determinants of Erythrocyte Membrane Fatty Acid Composition among Greenlanders |
topic_facet |
Research Article |
description |
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 ... |
format |
Text |
author |
Andersen, Mette Korre Jørsboe, Emil Sandholt, Camilla Helene Grarup, Niels Jørgensen, Marit Eika Færgeman, Nils Joakim Bjerregaard, Peter Pedersen, Oluf Moltke, Ida Hansen, Torben Albrechtsen, Anders |
author_facet |
Andersen, Mette Korre Jørsboe, Emil Sandholt, Camilla Helene Grarup, Niels Jørgensen, Marit Eika Færgeman, Nils Joakim Bjerregaard, Peter Pedersen, Oluf Moltke, Ida Hansen, Torben Albrechtsen, Anders |
author_sort |
Andersen, Mette Korre |
title |
Identification of Novel Genetic Determinants of Erythrocyte Membrane Fatty Acid Composition among Greenlanders |
title_short |
Identification of Novel Genetic Determinants of Erythrocyte Membrane Fatty Acid Composition among Greenlanders |
title_full |
Identification of Novel Genetic Determinants of Erythrocyte Membrane Fatty Acid Composition among Greenlanders |
title_fullStr |
Identification of Novel Genetic Determinants of Erythrocyte Membrane Fatty Acid Composition among Greenlanders |
title_full_unstemmed |
Identification of Novel Genetic Determinants of Erythrocyte Membrane Fatty Acid Composition among Greenlanders |
title_sort |
identification of novel genetic determinants of erythrocyte membrane fatty acid composition among greenlanders |
publisher |
Public Library of Science |
publishDate |
2016 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4920407/ http://www.ncbi.nlm.nih.gov/pubmed/27341449 https://doi.org/10.1371/journal.pgen.1006119 |
genre |
greenlander* |
genre_facet |
greenlander* |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4920407/ http://www.ncbi.nlm.nih.gov/pubmed/27341449 http://dx.doi.org/10.1371/journal.pgen.1006119 |
op_rights |
© 2016 Andersen et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
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CC-BY |
op_doi |
https://doi.org/10.1371/journal.pgen.1006119 |
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PLOS Genetics |
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