Polymorphisms in FADS1 and FADS2 alter desaturase activity in young Caucasian and Asian adults.

Autor: Merino DM; University of Guelph, Department of Human Health & Nutritional Sciences, Guelph, Canada N1G 2W1. dmerinod@uoguelph.ca, Johnston H, Clarke S, Roke K, Nielsen D, Badawi A, El-Sohemy A, Ma DW, Mutch DM
Jazyk: angličtina
Zdroj: Molecular genetics and metabolism [Mol Genet Metab] 2011 Jun; Vol. 103 (2), pp. 171-8. Date of Electronic Publication: 2011 Feb 23.
DOI: 10.1016/j.ymgme.2011.02.012
Abstrakt: Recent evidence indicates that genetic variation in fatty acid desaturases 1 and 2 (FADS1 and FADS2) is associated with changes in plasma fatty acid profiles; however, the association with altered desaturase activity has not been examined in different ethnic populations. The present study examined whether genetic variation in the FADS gene cluster regulates desaturase activity in two populations of young Canadian adults (Caucasian and Asian) and whether altered desaturase activity was reflected in both n-3 and n-6 fatty acid profiles. FADS1 and FADS2 were genotyped in a random subset of participants (Caucasian, n=78; Asian, n=69) from the Toronto Nutrigenomics and Health study using MALDI-TOF mass spectrometry, and plasma fatty acids were measured by gas chromatography. Desaturase activities were estimated using the following fatty acid ratios: γ-linoleic acid to linoleic acid (GLA:LA), arachidonic acid to linoleic acid (AA:LA), arachidonic acid to dihomo-γ-linoleic acid (AA:DGLA), and eicosapentaneoic acid to α-linolenic acid (EPA:ALA). Nineteen single nucleotide polymorphisms (SNPs) were examined, and several SNPs (9 in Caucasians and 8 in Asians) were associated with various desaturase activities. The most significant association detected was between the FADS1 rs174547 SNP and AA:LA in both Caucasians (p=4.0 × 10(-8)) and Asians (p=5.0 × 10(-5)). Although the minor allele for this SNP differed between Caucasians (T) and Asians (C), carriers of the C allele had a lower desaturase activity than carriers of the T allele in both groups. To determine whether rs174547 was a dominant SNP in the FADS gene cluster, we constructed an additional model which included this SNP as a covariate. Only one SNP (rs498793 in FADS2) remained associated with the EPA:ALA ratio (p=1.1 × 10(-5)) in Asians. This study shows that genetic variation in the FADS gene cluster (in particular rs174547) can alter desaturase activity in subjects of Caucasians and Asian descent.
(Copyright © 2010 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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