Genetic loci associated with plasma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium.

Autor: Rozenn N Lemaitre, Toshiko Tanaka, Weihong Tang, Ani Manichaikul, Millennia Foy, Edmond K Kabagambe, Jennifer A Nettleton, Irena B King, Lu-Chen Weng, Sayanti Bhattacharya, Stefania Bandinelli, Joshua C Bis, Stephen S Rich, David R Jacobs, Antonio Cherubini, Barbara McKnight, Shuang Liang, Xiangjun Gu, Kenneth Rice, Cathy C Laurie, Thomas Lumley, Brian L Browning, Bruce M Psaty, Yii-Der I Chen, Yechiel Friedlander, Luc Djousse, Jason H Y Wu, David S Siscovick, André G Uitterlinden, Donna K Arnett, Luigi Ferrucci, Myriam Fornage, Michael Y Tsai, Dariush Mozaffarian, Lyn M Steffen
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Zdroj: PLoS Genetics, Vol 7, Iss 7, p e1002193 (2011)
Druh dokumentu: article
ISSN: 1553-7390
1553-7404
DOI: 10.1371/journal.pgen.1002193
Popis: 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.
Databáze: Directory of Open Access Journals
Externí odkaz: