期刊
MOLECULAR GENETICS AND METABOLISM
卷 103, 期 2, 页码 171-178出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymgme.2011.02.012
关键词
FADS1; FADS2; Desaturase activity; Gene-association study; Plasma fatty acids; Gas chromatography
资金
- Advanced Food and Materials Network [460137]
- Ontario Ministry of Agriculture, Food and Rural Affairs [200032]
- Natural Sciences and Engineering Research Council [312062]
- Canada Foundation for Innovation
- Ontario Research Fund [17883]
Recent evidence indicates that genetic variation in fatty acid desaturases 1 and 2 (FADS! 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. FADS! 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: gamma-linoleic acid to linoleic acid (GLA:LA), arachidonic acid to linoleic acid (AA:LA), arachidonic acid to dihomo-gamma-linoleic acid (AA:DGLA), and eicosapentaneoic acid to alpha-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 x 10(-8)) and Asians (p = 5.0 x 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 x 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. (C) 2011 Elsevier Inc. All rights reserved.
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