Gene Expression of Desaturase (FADS1 and FADS2) and Elongase (ELOVL5) Enzymes in Peripheral Blood: Association with Polyunsaturated Fatty Acid Levels and Atopic Eczema in 4-Year-Old Children

Chisaguano, Aida Maribel; Montes, Rosa; Pérez-Berezo, Teresa; Castellote, Ana I.; Guerendiain, Marcela; Morales, Eva; García-Esteban, Raquel; Sunyer, Jordi; Franch, Àngels; López-Sabater, M. Carmen

doi:10.1371/journal.pone.0078245

Cited by 20 publications

(19 citation statements)

References 41 publications

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“…Genes with a H2H orientation are prone to co-expression and co-functionality33. Disturbed expression of the FADS genes has previously been reported in several IgE-mediated diseases, including asthma34 and atopic dermatitis3536, but this is the first such association with the direct cellular processes leading to IgE production. Variation in FADS gene expression during the activation time course is shown in supplementary Figure S3.…”

Section: Resultsmentioning

confidence: 85%

Global gene regulation during activation of immunoglobulin class switching in human B cells

Zhang

Fear

Willis‐Owen

et al. 2016

Sci Rep

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Immunoglobulin class switch recombination (CSR) to IgE is a tightly regulated process central to atopic disease. To profile the B-cell transcriptional responses underlying the activation of the germinal centre activities leading to the generation of IgE, naïve human B-cells were stimulated with IL-4 and anti-CD40. Gene expression and alternative splicing were profiled over 12 days using the Affymetrix Human Exon 1.0 ST Array. A total of 1,399 genes, forming 13 temporal profiles were differentially expressed. CCL22 and CCL17 were dramatically induced but followed a temporal trajectory distinct from classical mediators of isotype switching. AICDA, NFIL3, IRF4, XBP1 and BATF3 shared a profile with several genes involved in innate immunity, but with no recognised role in CSR. A transcription factor BHLHE40 was identified at the core of this profile. B-cell activation was also accompanied by variation in exon retention affecting >200 genes including CCL17. The data indicate a circadian component and central roles for the Th2 chemokines CCL22 and CCL17 in the activation of CSR.

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Section: Resultsmentioning

confidence: 85%

Global gene regulation during activation of immunoglobulin class switching in human B cells

Zhang

Fear

Willis‐Owen

et al. 2016

Sci Rep

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“…Likewise, genetic modulation by sex may be another relevant factor explaining some differences in the effect of the genetics of PUFA. Some PUFA are specifically required for reproduction [104]. It has been reported that PUFA concentrations are higher in females than in males during pregnancy and there are some studies showing sex-specific effects for some PUFA in determining several outcomes [68][69][70][71][72][73][74]140,141].…”

Section: Discussionmentioning

confidence: 99%

“…In Spain, the adherence to the Mediterranean diet pattern [99] is still relatively high in older subjects, but is decreasing in young people [100,101]. Although some studies specifically carried out in the Spanish Mediterranean population, have analyzed the association between several FADS and ELOVL candidate gene polymorphisms and PUFA concentrations [102][103][104][105][106], no study has investigated such associations at the GWAS level.…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Association Study for Serum Omega-3 and Omega-6 Polyunsaturated Fatty Acids: Exploratory Analysis of the Sex-Specific Effects and Dietary Modulation in Mediterranean Subjects with Metabolic Syndrome

et al. 2020

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Many early studies presented beneficial effects of polyunsaturated fatty acids (PUFA) on cardiovascular risk factors and disease. However, results from recent meta-analyses indicate that this effect would be very low or nil. One of the factors that may contribute to the inconsistency of the results is that, in most studies, genetic factors have not been taken into consideration. It is known that fatty acid desaturase (FADS) gene cluster in chromosome 11 is a very important determinant of plasma PUFA, and that the prevalence of the single nucleotide polymorphisms (SNPs) varies greatly between populations and may constitute a bias in meta-analyses. Previous genome-wide association studies (GWAS) have been carried out in other populations and none of them have investigated sex and Mediterranean dietary pattern interactions at the genome-wide level. Our aims were to undertake a GWAS to discover the genes most associated with serum PUFA concentrations (omega-3, omega-6, and some fatty acids) in a scarcely studied Mediterranean population with metabolic syndrome, and to explore sex and adherence to Mediterranean diet (MedDiet) interactions at the genome-wide level. Serum PUFA were determined by NMR spectroscopy. We found strong robust associations between various SNPs in the FADS cluster and omega-3 concentrations (top-ranked in the adjusted model: FADS1-rs174547, p = 3.34 × 10−14; FADS1-rs174550, p = 5.35 × 10−14; FADS2-rs1535, p = 5.85 × 10−14; FADS1-rs174546, p = 6.72 × 10−14; FADS2-rs174546, p = 9.75 × 10−14; FADS2-rs174576, p = 1.17 × 10−13; FADS2-rs174577, p = 1.12 × 10−12, among others). We also detected a genome-wide significant association with other genes in chromosome 11: MYRF (myelin regulatory factor)-rs174535, p = 1.49 × 10−12; TMEM258 (transmembrane protein 258)-rs102275, p = 2.43 × 10−12; FEN1 (flap structure-specific endonuclease 1)-rs174538, p = 1.96 × 10−11). Similar genome-wide statistically significant results were found for docosahexaenoic fatty acid (DHA). However, no such associations were detected for omega-6 PUFAs or linoleic acid (LA). For total PUFA, we observed a consistent gene*sex interaction with the DNTTIP2 (deoxynucleotidyl transferase terminal interacting protein 2)-rs3747965 p = 1.36 × 10−8. For adherence to MedDiet, we obtained a relevant interaction with the ME1 (malic enzyme 1) gene (a gene strongly regulated by fat) in determining serum omega-3. The top-ranked SNP for this interaction was ME1-rs3798890 (p = 2.15 × 10−7). In the regional-wide association study, specifically focused on the FADS1/FASD2/FADS3 and ELOVL (fatty acid elongase) 2/ELOVL 5 regions, we detected several statistically significant associations at p < 0.05. In conclusion, our results confirm a robust role of the FADS cluster on serum PUFA in this population, but the associations vary depending on the PUFA. Moreover, the detection of some sex and diet interactions underlines the need for these associations/interactions to be studied in all specific populations so as to better understand the complex metabolism of PUFA.

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“…This analysis also uncovers the pattern that odd-chain fatty acid residues are more abundant in the hearts of lean mice. These results are interpretable in terms of the aetiology of metabolic and heart disease [24,[41][42][43][44] in a manner that is orthogonal to the abundance analysis of whole lipids.…”

Section: Lipidome Analysismentioning

confidence: 99%

A high-throughput platform for detailed lipidomic analysis of a range of mouse and human tissues

et al. 2020

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Lipidomics is of increasing interest in studies of biological systems. However, high-throughput data collection and processing remains non-trivial, making assessment of phenotypes difficult. We describe a platform for surveying the lipid fraction for a range of tissues. These techniques are demonstrated on a set of seven different tissues (serum, brain, heart, kidney, adipose, liver, and vastus lateralis muscle) from post-weaning mouse dams that were either obese (> 12 g fat mass) or lean (<5 g fat mass). This showed that the lipid metabolism in some tissues is affected more by obesity than others. Analysis of human serum (healthy nonpregnant women and pregnant women at 28 weeks' gestation) showed that the abundance of several phospholipids differed between groups. Human placenta from mothers with high and low BMI showed that lean placentae contain less polyunsaturated lipid. This platform offers a way to map lipid metabolism with immediate application in metabolic research and elsewhere.

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Gene Expression of Desaturase (FADS1 and FADS2) and Elongase (ELOVL5) Enzymes in Peripheral Blood: Association with Polyunsaturated Fatty Acid Levels and Atopic Eczema in 4-Year-Old Children

Cited by 20 publications

References 41 publications

Global gene regulation during activation of immunoglobulin class switching in human B cells

Global gene regulation during activation of immunoglobulin class switching in human B cells

Genome-Wide Association Study for Serum Omega-3 and Omega-6 Polyunsaturated Fatty Acids: Exploratory Analysis of the Sex-Specific Effects and Dietary Modulation in Mediterranean Subjects with Metabolic Syndrome

A high-throughput platform for detailed lipidomic analysis of a range of mouse and human tissues

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