Abstract
The objective was to test whether FFAR4 single nucleotide polymorphisms (SNPs) are associated with glycemic control-related traits in humans following fish oil supplementation. A total of 210 participants were given 3 g/day of omega-3 (n-3) fatty acids (FA) (1.9–2.2 g of eicosapentaenoic acid (EPA) and 1.1 g of docosahexaenoic acid (DHA)) during six weeks. Biochemical parameters were taken before and after the supplementation. Using the HapMap database and the tagger procedure in Haploview, 12 tagging SNPs in FFAR4 were selected and then genotyped using TaqMan technology. Transcript expression levels were measured for 30 participants in peripheral mononuclear blood cells. DNA methylation levels were measured for 35 participants in leukocytes. In silico analyses were also performed. Four gene–diet interactions on fasting insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) index values were found. rs17108973 explained a significant proportion of the variance of insulin levels (3.0%) and HOMA-IR (2.03%) index values. Splice site prediction was different depending on the allele for rs11187527. rs17108973 and rs17484310 had different affinity for transcription factors depending on the allele. n-3 FAs effectively improve insulin-related traits for major allele homozygotes of four FFAR4 SNPs as opposed to carriers of the minor alleles.
Highlights
Insulin resistance is a condition in which the response of sensitive tissues to insulin as well as glucose uptake are decreased [1]
Insulin resistance is a predictor of type 2 diabetes mellitus (T2DM), and individuals affected with T2DM have a higher cardiovascular risk [2]
No LD between studied single nucleotide polymorphisms (SNPs) neither other SNPs located in coding regions, nor SNPs previously identified in a genome-wide association study (GWAS) was observed
Summary
Insulin resistance is a condition in which the response of sensitive tissues to insulin as well as glucose uptake are decreased [1]. Insulin resistance is a predictor of type 2 diabetes mellitus (T2DM), and individuals affected with T2DM have a higher cardiovascular risk [2]. Given that T2DM and cardiovascular diseases are major public health concerns worldwide, and especially in North America, where 40 million people are going to be affected by 2030, there is an urgent need to find new strategies to prevent the onset of T2DM, [3]. An omega-3 (n-3) fatty acid (FA) supplementation may exert beneficial effects on T2DM and cardiovascular risk, among others because n-3 FAs have the capacity to bind to the free fatty acid receptor 4 (FFAR4) [4]. FFAR4, commonly referred to G protein-coupled receptor 120 (GPR120), is a gene encoding for a protein that acts as a receptor for free fatty acids (FFAs) [5].
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