Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from α-linolenic acid (ALA) by elongation and desaturation. We investigated the association of common genetic variation with plasma phospholipid levels of the four major n-3 PUFAs by performing genome-wide association studies in five population-based cohorts comprising 8,866 subjects of European ancestry. Minor alleles of SNPs in FADS1 and FADS2 (desaturases) were associated with higher levels of ALA (p = 3 x 10⁻⁶⁴) and lower levels of eicosapentaenoic acid (EPA, p = 5 x 10⁻⁵⁸) and docosapentaenoic acid (DPA, p = 4 x 10⁻¹⁵⁴). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p = 2 x 10⁻¹²) and DPA (p = 1 x 10⁻⁴³) and lower docosahexaenoic acid (DHA, p = 1 x 10⁻¹⁵). In addition to genes in the n-3 pathway, we identified a novel association of DPA with several SNPs in GCKR (glucokinase regulator, p = 1 x 10⁻⁸). We observed a weaker association between ALA and EPA among carriers of the minor allele of a representative SNP in FADS2 (rs1535), suggesting a lower rate of ALA-to-EPA conversion in these subjects. In samples of African, Chinese, and Hispanic ancestry, associations of n-3 PUFAs were similar with a representative SNP in FADS1 but less consistent with a representative SNP in ELOVL2. Our findings show that common variation in n-3 metabolic pathway genes and in GCKR influences plasma phospholipid levels of n-3 PUFAs in populations of European ancestry and, for FADS1, in other ancestries.

Genetic Loci Associated with Plasma Phospholipid n-3 Fatty Acids: A Meta-Analysis of Genome-wide Association Studies from the CHARGE Consortium / Lemaitre, R.; Tanaka, T.; Weihong, T.; Manichaikul, A.; Foy, M.; Kabagambe, K. E.; Nettleton, J. A.; King, I. B.; Weng, L. C.; Bhattacharya, S.; Bandinelli, S.; Bis, J. C.; Rich, S. S.; Jacobs, D. R. J. r.; Cherubini, Antonio; Mcknight, B.; Liang, S.; Gu, X.; Rice, K.; Laurie, C. C.; Lumley, T.; Browning, B. L.; Psaty, B. M.; Chen, Y. I.; Friedlander, Y.; Djousse, L.; Wu, J. H. Y.; Siscovick, D. S.; Uitterlinden, A. G.; Arnett, D. K.; Ferrucci, L.; Fornage, M.; Tsai, M. Y.; Mozaffarian, D.; Steffen, L. M.. - In: PLOS GENETICS. - ISSN 1553-7390. - STAMPA. - 7:e1002193(2011). [10.1371/journal.pgen.1002193]

Genetic Loci Associated with Plasma Phospholipid n-3 Fatty Acids: A Meta-Analysis of Genome-wide Association Studies from the CHARGE Consortium

CHERUBINI, Antonio;
2011-01-01

Abstract

Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from α-linolenic acid (ALA) by elongation and desaturation. We investigated the association of common genetic variation with plasma phospholipid levels of the four major n-3 PUFAs by performing genome-wide association studies in five population-based cohorts comprising 8,866 subjects of European ancestry. Minor alleles of SNPs in FADS1 and FADS2 (desaturases) were associated with higher levels of ALA (p = 3 x 10⁻⁶⁴) and lower levels of eicosapentaenoic acid (EPA, p = 5 x 10⁻⁵⁸) and docosapentaenoic acid (DPA, p = 4 x 10⁻¹⁵⁴). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p = 2 x 10⁻¹²) and DPA (p = 1 x 10⁻⁴³) and lower docosahexaenoic acid (DHA, p = 1 x 10⁻¹⁵). In addition to genes in the n-3 pathway, we identified a novel association of DPA with several SNPs in GCKR (glucokinase regulator, p = 1 x 10⁻⁸). We observed a weaker association between ALA and EPA among carriers of the minor allele of a representative SNP in FADS2 (rs1535), suggesting a lower rate of ALA-to-EPA conversion in these subjects. In samples of African, Chinese, and Hispanic ancestry, associations of n-3 PUFAs were similar with a representative SNP in FADS1 but less consistent with a representative SNP in ELOVL2. Our findings show that common variation in n-3 metabolic pathway genes and in GCKR influences plasma phospholipid levels of n-3 PUFAs in populations of European ancestry and, for FADS1, in other ancestries.
2011
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11566/330356
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