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The association of fatty acid desaturase gene polymorphisms on long-chain polyunsaturated fatty acid composition in Indonesian infants.

ABSTRACT: Background:Adequate availability of long-chain polyunsaturated fatty acids (LC-PUFAs) is important for human health from pregnancy to adulthood. Previous studies on fatty acid desaturase (FADS) gene single-nucleotide polymorphisms (SNPs) have been performed predominantly in Western populations and showed that FADS SNPs had a marked impact on LC-PUFA composition in blood and tissues. Objectives:We aimed to investigate the influence of fetal FADS genotypes on LC-PUFA composition in umbilical artery plasma lipids in Indonesian infants. Design:We performed a cross-sectional study to assess for these associations. Results:A total of 12 cord plasma n-6 (?-6) and n-3 (?-3) fatty acids were analyzed for associations with 18 FADS gene cluster SNPs from 390 women with single parturition from the Indonesian Prospective Study of Atopic Dermatitis in Infants (ISADI). Fetal FADS genotypes influenced cord plasma LC-PUFA composition, but, in contrast to previous studies from Western populations, the quantitatively predominant SNPs were associated with lower LC-PUFA content. Conclusion:To our knowledge, this study was the first in South East Asia on FADS genotypes and arterial cord blood fatty acids to show an association between fetal LC-PUFA composition and fetal FADS SNPs. The FADS genotype distribution differs markedly between different geographical populations. This trial was registered at clinicaltrials.gov as NCT02401178.

SUBMITTER: Tanjung C

PROVIDER: S-EPMC6250987 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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The association of fatty acid desaturase gene polymorphisms on long-chain polyunsaturated fatty acid composition in Indonesian infants.

Tanjung Conny C Rzehak Peter P Sudoyo Herawati H Mansyur Muchtaruddin M Munasir Zakiudin Z Immanuel Suzanna S Irawan Roedi R Reischl Eva E Demmelmair Hans H Hadinegoro Sri Rezeki SR Sjarif Damayanti Rusli DR Koletzko Berthold B

The American journal of clinical nutrition 20181101 5

<h4>Background</h4>Adequate availability of long-chain polyunsaturated fatty acids (LC-PUFAs) is important for human health from pregnancy to adulthood. Previous studies on fatty acid desaturase (FADS) gene single-nucleotide polymorphisms (SNPs) have been performed predominantly in Western populations and showed that FADS SNPs had a marked impact on LC-PUFA composition in blood and tissues.<h4>Objectives</h4>We aimed to investigate the influence of fetal FADS genotypes on LC-PUFA composition in ...[more]

PMID: 30475958

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Project description:BackgroundIn randomized trials, supplementation of n-3 (ω-3) long-chain polyunsaturated fatty acids (LC-PUFAs) during pregnancy has resulted in increased size at birth, which is attributable to longer gestation.ObjectiveWe examined this finding by using a Mendelian randomization approach utilizing fatty acid desaturase (FADS) gene variants affecting LC-PUFA metabolism.DesignAs part of a tri-ethnic mother-offspring cohort in Singapore, 35 genetic variants in FADS1, FADS2, and FADS3 were genotyped in 898 mothers and 1103 offspring. Maternal plasma n-3 and n-6 PUFA concentrations at 26-28 wk of gestation were measured. Gestation duration was derived from an ultrasound dating scan in early pregnancy and from birth date. Birth length and weight were measured. Eight FADS variants were selected through a tagging-SNP approach and examined in association with PUFA concentrations, gestation duration among spontaneous labors, and birth size with the use of ethnicity-adjusted linear regressions and survival models that accounted for the competing risks of induced labor and prelabor cesarean delivery.ResultsMaternal FADS1 variant rs174546, tagging for 8 other variants located on FADS1 and FADS2, was strongly related to plasma n-6 but not n-3 LC-PUFA concentrations. Offspring and maternal FADS3 variants were associated with gestation duration among women who had spontaneous labor: each copy of rs174450 minor allele C was associated with a shorter gestation by 2.2 d (95% CI: 0.9, 3.4 d) and 1.9 d (0.7, 3.0 d) for maternal and offspring variants, respectively. In survival models, rs174450 minor allele homozygotes had reduced time to delivery after spontaneous labor compared with major allele homozygotes [HR (95% CI): 1.51 (1.18, 1.95) and 1.51 (1.20, 1.89) for mothers and offspring, respectively].ConclusionsWith the use of a Mendelian randomization approach, we observed associations between FADS variants and gestation duration. This suggests a potential role of LC-PUFAs in gestation duration. This trial was registered at http://www.clinicaltrials.gov as NCT01174875.

Project description:Both pre- and early postnatal supplementation with docosahexaenoic acid (DHA), arachidonic acid (AA) and folate have been related to neural development, but their long-term effects on later neural function remain unclear. We evaluated the long-term effects of maternal prenatal supplementation with fish-oil (FO), 5-methyltetrahydrofolate (5-MTHF), placebo or FO + 5-MTHF, as well as the role of fatty acid desaturase (FADS) gene cluster polymorphisms, on their offspring's processing speed at later school age. This study was conducted in NUHEAL children at 7.5 (n = 143) and 9 years of age (n = 127). Processing speed tasks were assessed using Symbol Digit Modalities Test (SDMT), Children Color Trails Test (CCTT) and Stroop Color and Word Test (SCWT). Long-chain polyunsaturated fatty acids, folate and total homocysteine (tHcy) levels were determined at delivery from maternal and cord blood samples. FADS and methylenetetrahydrofolate reductase (MTHFR) 677 C > T genetic polymorphisms were analyzed. Mixed models (linear and logistic) were performed. There were significant differences in processing speed performance among children at different ages (p < 0.001). The type of prenatal supplementation had no effect on processing speed in children up to 9 years. Secondary exploratory analyses indicated that children born to mothers with higher AA/DHA ratio at delivery (p < 0.001) and heterozygotes for FADS1 rs174556 (p < 0.05) showed better performance in processing speed at 9 years. Negative associations between processing speed scores and maternal tHcy levels at delivery were found. Our findings suggest speed processing development in children up to 9 years could be related to maternal factors, including AA/DHA and tHcy levels, and their genetic background, mainly FADS polymorphism. These considerations support that maternal prenatal supplementation should be quantitatively adequate and individualized to obtain better brain development and mental performance in the offspring.

Project description:BackgroundPolyunsaturated fatty acids (PUFAs) are associated with a lower risk of multiple diseases. Fatty acid desaturase 1 gene (FADS1) polymorphisms and dietary PUFA intake are both established determinants of circulating PUFA proportions.ObjectiveWe explored the joint effects of FADS1 polymorphisms and dietary PUFA intake on circulating PUFA proportions.DesignWe studied 2288 participants from a nested case-control study of coronary artery disease among participants who provided blood samples in the Nurses' Health Study and the Health Professionals Follow-Up Study. Dietary PUFA intake was obtained from semiquantitative food-frequency questionnaires. FADS1 rs174546 was genotyped by using the Affymetrix 6.0 platform, and circulating PUFA proportions were measured with gas-liquid chromatography. Linear regression models were used to examine the associations between rs174546 and circulating proportions of each fatty acid. Gene-diet interactions were tested by including a cross-product term of dietary intake of each PUFA by rs174546 genotype in the linear regression models.ResultsAfter adjustment for sex and ancestry, each copy of the C allele of rs174546 was associated with higher circulating proportions of arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) and lower proportions of linoleic acid and α-linolenic acid. The magnitude of positive association between higher consumption of dietary EPA or DHA and circulating proportions of EPA increased with each copy of the rs174546_T allele (P-interaction = 0.01 and 0.007, respectively). Each 1-SD increment in EPA intake was associated with an average 3.7% increase in circulating EPA proportions among participants with the rs174546_CC genotype and an average 7.8% increase among participants with the TT genotype.ConclusionsCarriers of the T allele at FADS1 rs174546 may need higher doses of dietary EPA and DHA to achieve the same circulating proportions of EPA as carriers of the C allele. The implications of these findings on disease risk and dietary guidelines require further study.

Project description:Docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (ARA, 20:4n-6) are the major long chain polyunsaturated fatty acids (LCPUFA) of the central nervous system. We examined the alterations in transcriptional profiles in neonate baboon cerebral cortex brain tissue using high-density Affymetrix oligonucleotide arrays ("U133 plus 2.0"). Twelve neonates were divided into 3 groups: Control (C, no DHA-ARA); 1× LCPUFA (L, 0.33%DHA-0.67%ARA); 3× LCPUFA (L3, 1.00%DHA-0.67%ARA). Significance analysis (P < 0.05) of a total of >54,000 probe sets (ps) identified changes in expression levels of 1108 ps, representing 2.05% of the total ps on the oligoarray, with most ps showing <2-fold change. Comparing L and C, 534 ps were upregulated with supplementation, and 574 ps were downregulated. For the L3/C comparisons, 666 ps were upregulated and 442 ps were downregulated. Characterization of differentially regulated genes by gene ontology assign them to diverse biological functions, notably lipid metabolism, ion channel and transport, G-protein and signal transduction, development, visual perception, membrane function, apoptosis, cytoskeleton, peptidases, cell cycle, stress response, kinases and phosphatases, transcription regulation, receptors, and ubiquitin, with about 400 transcripts having no defined function. Of differentially expressed genes involved in lipid metabolism, PLA2G6, a phospholipase recently associated with infantile neuroaxonal dystrophy, was downregulated in both LCPUFA groups. ELOVL5, a PUFA elongase, was the only enzyme in the LCPUFA biosynthetic pathway that was differentially expressed. Mitochondrial fatty acid carrier, CPT2, was among several genes associated with mitochondrial fatty acid oxidation to be downregulated, while the mitochondrial proton carrier, UCP2, was upregulated. PUFA-regulated receptor, Retinoic acid receptor alpha (RARA) was repressed in both groups, while HNF4A, a PUFA regulated factor, was downregulated in L3/C. Genes involved in neural development, TIMM8A, NRG1, SEMA3D and NUMB, were upregulated while HES1 and SIM1 showed decreased expression. LUM, EML2, TIMP3 and TTC8 which have roles in visual perception were upregulated and TIA1, a silencer of COX2 gene translation is upregulated in L3/C. Ingenuity network analysis identified a top network associated with nervous system development and function with EGFR as the outstanding interaction partner. In this network EGFR interacts with genes involved in neural or visual perception, TIMP3, NRG1, ADAM17, EDG7 and FGF7. Quantitative real time-PCR analysis on selected genes confirmed the array results. The L and L3 groups have DHA and ARA content within the ranges observed in human and baboon breastmilk, and thus these data indicate that LCPUFA concentrations within the normal range of human breastmilk induce global changes in gene expression across numerous functions including transcripts involved in neural development, visual perception, etc. Keywords: dietary dose response

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The association of fatty acid desaturase gene polymorphisms on long-chain polyunsaturated fatty acid composition in Indonesian infants.

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The association of fatty acid desaturase gene polymorphisms on long-chain polyunsaturated fatty acid composition in Indonesian infants.

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