Polyunsaturated fatty acids (PUFA) influence many physiological functions. Associations have been found between single nucleotide polymorphisms (SNP) in the FADS1 (Fatty acid desaturase 1) gene and the relative abundance of PUFA in serum lipids. This study examines the relationship between two SNPs in the FADS1 gene (rs174546, rs174537) and the fatty acid (FA) composition of serum lipids in adolescents (13-18 years). We used DNA samples (670 children; 336 girls and 334 boys) from the Childhood Obesity Prevalence and Treatment (COPAT) project. Genomic DNA was extracted from peripheral blood leukocytes in whole blood samples. For genotype analysis, TaqMan SNP Genotyping assays (Applied Biosystems) were used. Fatty acid composition of serum lipids was assessed using gas chromatography. The T-statistic and regression were used for statistical evaluations. Minor allele T carriers in both SNPs had significant lower level of palmitic acid (16:0, phospholipids) and arachidonic acid (20:4[n-6], phospholipids) in both sexes. In girls, we found a significant positive association between minor allele T carriers and eicosadienoic acid (20:2[n-6], cholesteryl esters) in both SNPs. Being a minor allele T carrier was significantly positively associated with dihomo-γ-linolenic acid (20:3[n-6], phospholipids) in boys in both SNPs. SNPs (including rs174546, rs174537) in the FADS gene cluster should have impacted desaturase activity, which may contribute to different efficiency of PUFA synthesis.

1st Medical Faculty Charles University Prague The Czech Republic

4th Department of Internal Medicine 1st Medical Faculty Charles University Prague The Czech Republic

Institute of Endocrinology Prague The Czech Republic

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Aldhoon-Hainerová I, Zamrazilová H, Atkinson RL, Dušátková L, Sedláčková B, Hlavatý P, et al. Clinical and laboratory characteristics of 1179 Czech adolescents evaluated for antibodies to human adenovirus 36. Int J Obes (Lond). 2014;38:285-91. https://doi.org/10.1038/ijo.2013.72

Alonso DL, Garcia-Maroto F, Rodriguez-Ruiz J, Garrido JA, Vilches MA. Evolution of the membrane-bound fatty acid desaturases. Biochem Syst Ecol. 2003;31:1111-24. https://doi.org/10.1016/S0305-1978(03)00041-3

Baylin A, Campos H. Arachidonic acid in adipose tissue is associated with nonfatal acute myocardial infarction in the central valley of Costa Rica. J Nutr. 2004;134:3095-9. https://doi.org/10.1093/jn/134.11.3095

Bergström S, Danielsson H, Klenberg D, Samuelsson B. The enzymatic conversion of essential fatty acids into prostaglandins (prostaglandins and related factors 34). J Biol Chem. 1964;239:PC4006-8.

Bernert JT Jr, Sprecher H. Studies to determine the role rates of chain elongation and desaturation play in regulating the unsaturated fatty acid composition of rat liver lipids. Biochim Biophys Acta. 1975;398:354-63. https://doi.org/10.1016/0005-2760(75)90186-1

Bokor S, Dumont J, Spinneker A, Gonzalez-Gross M, Nova E, Widhalm K, et al. Single nucleotide polymorphisms in the FADS gene cluster are associated with delta-5 and delta-6 desaturase activities estimated by serum fatty acid ratios. J Lipid Res. 2010;51:2325-33. https://doi.org/10.1194/jlr.M006205

Brenna JT, Salem N Jr, Sinclair AJ, Cunnane SC. α-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans. Prostaglandins Leukot Essent Fatty Acids. 2009;80:85-91. https://doi.org/10.1073/pnas.251516598

Buist PH. Fatty acid desaturases: selecting the dehydrogenation channel. Nat Prod Rep. 2004;21:249-62. https://doi.org/10.1039/b302094k

Caspi A, Williams B, Kim-Cohen J, Craig IW, Milne BJ, Poulton R, et al. Moderation of breastfeeding effects on the IQ by genetic variation in fatty acid metabolism. Proc Natl Acad Sci. 2007;104:18860-5. https://doi.org/10.1073/pnas.0704292104

Ching YK, Chin YS, Appukutty M, Ramanchadran V, Yu CY, Ang GY, et al. Interaction of dietary linoleic acid and α-linolenic acids with rs174547 in FADS1 gene on metabolic syndrome components among vegetarians. Nutrients. 2019;11:1686. https://doi.org/10.3390/nu11071686

Coetzer H, Claassen N, Van Papendorp DH, Kruger MC. Calcium transport by isolated brush border and basolateral membrane vesicles: role of essential fatty acid supplementation. Prostaglandins Leukot Essent Fatty Acids. 1994;50:257-66. https://doi.org/10.1016/0952-3278(94)90164-3

Coltell O, Sorlí JV, Asensio EM, Barragán R, González JI, Giménez-Alba IM, et al. 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. Nutrients. 2020;12:310. https://doi.org/10.3390/nu12020310

Das UN. Essential fatty acids: biochemistry, physiology and pathology. Biotechnol J Healthcare Nutr Technol. 2006;1:420-39. https://doi.org/10.1002/biot.200600012

dbSNP. Genotype frequency (NIH) rs174546. 10 Apr 2021a. https://www.ncbi.nlm.nih.gov/snp/rs174546#frequency_tab. Accessed 21 Apr 2021.

dbSNP. Genotype frequency (NIH) rs174537. 10 Apr 2021b. https://www.ncbi.nlm.nih.gov/snp/rs174537#frequency_tab. Accessed 21 Apr 2021.

Deo RC, Reich D, Tandon A, Akylbekova E, Patterson N, Waliszewska A, et al. Genetic differences between the determinants of lipid profile phenotypes in African and European Americans: the Jackson heart study. PLoS Genet. 2009;5:e1000342. https://doi.org/10.1371/journal.pgen.1000342

Dumont J, Huybrechts I, Spinneker A, Gottrand F, Grammatikaki E, Bevilacqua N, et al. FADS1 genetic variability interacts with dietary α-linolenic acid intake to affect serum non-HDL-cholesterol concentrations in European adolescents. J Nutr. 2011;141:1247-53. https://doi.org/10.3945/jn.111.140392

Elmendorf JS. Fluidity of insulin action. Mol Biotechnol. 2004;27:127-38. https://doi.org/10.1073/pnas.77.2.915

FADS1. FADS1 fatty acid desaturase 1 [Homo sapiens (human)]. 4 Oct 2020. https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=DetailsSearch&Term=3992. Accessed 12 Oct 2020.

FADS2. FADS2 fatty acid desaturase 2 [Homo sapiens (human)]. 4 Oct 2020. https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=DetailsSearch&Term=9415. Accessed 12 Oct 2020.

Fisk, HL, West, AL,Childs, CE, Burdge, BC, Clader, PC. The use of gas chromatography to analyze compositional changes of fatty acids in rat liver tissue during pregnancy. J Vis Exp 2014;13(85):51445. https://doi.org/10.3791/51445

Fothergill, W.T. Gas chromatography. Technique. Proc R Soc Med. 1968;61(5):525-8.

Glaser C, Heinrich J, Koletzko B. Role of FADS1 and FADS2 polymorphisms in polyunsaturated fatty acid metabolism. Metabolism. 2010;59:993-9. https://doi.org/10.1016/j.metabol.2009.10.022

Haas GM, Liepold E, Schwandt P. Percentile curves for fat patterning in German adolescents. World J Pediatr. 2011;7:16-23. https://doi.org/10.1007/s12519-011-0241-4

Hallmann J, Kolossa S, Gedrich K, Celis-Morales C, Forster H, O'Donovan CB, et al. Predicting fatty acid profiles in blood based on food intake and the FADS1 rs174546 SNP. Mol Nutr Food Res. 2015;59:2565-73. https://doi.org/10.1002/mnfr.201500414

Hastings N, Agaba M, Tocher DR, Leaver MJ, Dick JR, Sargent JR, et al. A vertebrate fatty acid desaturase with Δ5 and Δ6 activities. Proc Natl Acad Sci. 2001;98:14304-9. https://doi.org/10.1073/pnas.251516598

Idf.org. (2021). International Diabetes Federation - Home. 9 Apr 2021. https://www.idf.org/. Accessed 10 Apr 2021.

Issemann I, Prince R, Tugwood J, Green S. A role for fatty acids and liver fatty acid binding protein in peroxisome proliferation? Biochem Soc Trans. 1992;20:824-7. https://doi.org/10.1042/bst0200824

Jump DB, Botolin D, Wang Y, Xu J, Christian B, Demeure O. Fatty acid regulation of hepatic gene transcription. J Nutr. 2005;135:2503-6. https://doi.org/10.1093/jn/135.11.2503

Kark JD, Kaufmann NA, Binka F, Goldberger N, Berry EM. Adipose tissue n-6 fatty acids and acute myocardial infarction in a population consuming a diet high in polyunsaturated fatty acids. Am J Clin Nutr. 2003;77:796-802. https://doi.org/10.1093/ajcn/77.4.796

Klingel SL, Valsesia A, Astrup A, Kunesova M, Saris WH, Langin D, et al. FADS1 genotype is distinguished by human subcutaneous adipose tissue fatty acids, but not inflammatory gene expression. Int J Obes (Lond). 2019;43:1539-48. https://doi.org/10.1038/s41366-018-0169-z

Kobzová J, Vignerová J, Bláha P, Krejcovský L, Riedlová J. The 6th nationwide anthropological survey of children and adolescents in The Czech Republic in 2001. Cent Eur J Public Health. 2004;12:126-30.

Koletzko B, Reischl E, Tanjung C, Gonzalez-Casanova I, Ramakrishnan U, Meldrum S, et al. FADS1 and FADS2 polymorphisms modulate fatty acid metabolism and dietary impact on health. Annu Rev Nutr. 2019;39:21-44. https://doi.org/10.1146/annurev-nutr-082018-124250.

Kröger J, Schulze MB. Recent insights into the relation of Δ5 desaturase and Δ6 desaturase activity to the development of type 2 diabetes. Curr Opin Lipidol. 2012;23:4-10. https://doi.org/10.1097/MOL.0b013e32834d2dc5

Lands WE. Biochemistry and physiology of n-3 fatty acids. FASEB J. 1992;6:2530-6. https://doi.org/10.1096/fasebj.6.8.1592205

Lankinen MA, Fauland A, Shimizu BI, Ågren J, Wheelock CE, Laakso M, et al. Inflammatory response to dietary linoleic acid depends on FADS1 genotype. Am J Clin Nutr. 2019;109:165-75. https://doi.org/10.1093/ajcn/nqy287

Lattka E, Illig T, Koletzko B, Heinrich J. Genetic variants of the FADS1 FADS2 gene cluster as related to essential fatty acid metabolism. Curr Opin Lipidol. 2010;21:64-9. https://doi.org/10.1097/MOL.0b013e3283327ca8

Merino DM, Johnston H, Clarke S, Roke K, Nielsen D, Badawi A, et al. W L., Mutch, D. M. polymorphisms in FADS1 and FADS2 alter desaturase activity in young Caucasian and Asian adults. Mol Genet Metab. 2011;103:171-8. https://doi.org/10.1016/j.ymgme.2011.02.012

Murphy AM, Lyons CL, Finucane OM, Roche HM. Interactions between differential fatty acids and inflammatory stressors-impact on metabolic health. Prostaglandins Leukot Essent Fatty Acids. 2015;92:49-55. https://doi.org/10.1016/j.plefa.2014.05.003

Nakamura MT, Cho HP, Clarke SD. Regulation of hepatic Δ-6 desaturase expression and its role in the polyunsaturated fatty acid inhibition of fatty acid synthase gene expression in mice. J Nutr. 2000;130:1561-5. https://doi.org/10.1093/jn/130.6.1561

Nakayama K, Bayasgalan T, Tazoe F, Yanagisawa Y, Gotoh T, Yamanaka K, et al. Jichi Medical University promotion team of a large-scale human genome Bank for all over Japan. A single nucleotide polymorphism in the FADS1/FADS2 gene is associated with plasma lipid profiles in two genetically similar Asian ethnic groups with distinctive differences in lifestyle. Hum Genet. 2010;127:685-90. https://doi.org/10.1007/s00439-010-0815-6

Pilch PF, Thompson PA, Czech MP. Coordinate modulation of D-glucose transport activity and bilayer fluidity in plasma membranes derived from control and insulin-treated adipocytes. Proc Natl Acad Sci. 1980;77:915-8. https://doi.org/10.1073/pnas.77.2.915

Rapoport SI, Igarashi M, Gao F. Quantitative contributions of diet and liver synthesis to docosahexaenoic acid homeostasis. Prostaglandins Leukot Essent Fatty Acids. 2010;82:273-6. https://doi.org/10.1016/j.plefa.2010.02.015

Roke K, Ralston JC, Abdelmagid S, Nielsen DE, Badawi A, El-Sohemy A, et al. Variation in the FADS1/2 gene cluster alters plasma n-6 PUFA and is weakly associated with hsCRP levels in healthy young adults. Prostaglandins Leukot Essent Fatty Acids. 2013;89:257-63. https://doi.org/10.1016/j.plefa.2013.06.003

Rzehak P, Heinrich J, Klopp N, Schaeffer L, Hoff S, Wolfram G, et al. Evidence for an association between genetic variants of the fatty acid desaturase 1 fatty acid desaturase 2 ( FADS1 FADS2) gene cluster and the fatty acid composition of erythrocyte membranes. Br J Nutr. 2009;101:20-6. https://doi.org/10.1017/S0007114508992564

Rzehak P, Thijs C, Standl M, Mommers M, Glaser C, Jansen E, et al. Variants of the FADS1 FADS2 gene cluster, blood levels of polyunsaturated fatty acids and eczema in children within the first 2 years of life. PLoS One. 2010;5:e13261. https://doi.org/10.1371/journal.pone.0013261

Sabatti C, Service SK, Hartikainen AL, Pouta A, Ripatti S, Brodsky J, et al. Genome-wide association analysis of metabolic traits in a birth cohort from a founder population. Nat Genet. 2009;41:35-46. https://doi.org/10.1038/ng.271

Schaeffer L, Gohlke H, Müller M, Heid IM, Palmer LJ, Kompauer I, et al. Common genetic variants of the FADS1 FADS2 gene cluster and their reconstructed haplotypes are associated with the fatty acid composition in phospholipids. Hum Mol Genet. 2006;15:1745-56. https://doi.org/10.1093/hmg/ddl117

Sergeant S, Hugenschmidt CE, Rudock ME, Ziegler JT, Ivester P, Ainsworth HC, et al. Differences in arachidonic acid levels and fatty acid desaturase (FADS) gene variants in African Americans and European Americans with diabetes or the metabolic syndrome. Br J Nutr. 2012;107:547-55. https://doi.org/10.1017/S0007114511003230

Smink W, Gerrits WJJ, Gloaguen M, Ruiter A, Van Baal J. Linoleic and α-linolenic acid as precursor and inhibitor for the synthesis of long-chain polyunsaturated fatty acids in liver and brain of growing pigs. Animal. 2012;6:262-70. https://doi.org/10.1017/S1751731111001479

Sperling P, Ternes P, Zank TK, Heinz E. The evolution of desaturases. Prostaglandins Leukot Essent Fatty Acids. 2003;68:73-95. https://doi.org/10.1016/s0952-3278(02)00258-2

Steer CD, Smith GD, Emmett PM, Hibbeln JR, Golding J. FADS2 polymorphisms modify the effect of breastfeeding on child IQ. PLoS One. 2010;5:e11570. https://doi.org/10.1371/journal.pone.0011570

Steffen LM, Vessby B, Jacobs DR, Steinberger J, Moran A, Hong CP, et al. Serum phospholipid and cholesteryl ester fatty acids and estimated desaturase activities are related to overweight and cardiovascular risk factors in adolescents. Int J Obes (Lond). 2008;32:1297-304. https://doi.org/10.1038/ijo.2008.89

Tanaka T, Shen J, Abecasis GR, Kisialiou A, Ordovas JM, Guralnik JM, et al. Genome-wide association study of plasma polyunsaturated fatty acids in the InCHIANTI study. PLoS Genet. 2009;5:e1000338. https://doi.org/10.1371/journal.pgen.1000338

Tarnowski M, Malinowski D, Pawlak K, Dziedziejko V, Safranow K, Pawlik A. GCK, GCKR, FADS1, DGKB/TMEM195 and CDKAL1 gene polymorphisms in women with gestational diabetes. Can J Diabetes. 2017;41:372-9. https://doi.org/10.1016/j.jcjd.2016.11.009

Truong H, DiBello JR, Ruiz-Narvaez E, Kraft P, Campos H, Baylin A. Does genetic variation in the Δ 6-desaturase promoter modify the association between α-linolenic acid and the prevalence of metabolic syndrome? Am J Clin Nutr. 2009;89:920-5. https://doi.org/10.3945/ajcn.2008.27107

Tvrzická E, Vecka M, Staňková B, Žák A. Analysis of fatty acids in plasma lipoproteins by gas chromatography-flame ionization detection: quantitative aspects. Anal Chim Acta. 2002;465:337-50. https://doi.org/10.1016/S0003-2670(02)00396-3

Wang L, Athinarayanan S, Jiang G, Chalasani N, Zhang M, Liu W. Fatty acid desaturase 1 gene polymorphisms control human hepatic lipid composition. Hepatology. 2015;61:119-28. https://doi.org/10.1002/hep.27373

Wolters M, Dering C, Siani A, Russo P, Kaprio J, Rise P, et al. The role of a FADS1 polymorphism in the association of fatty acid blood levels, BMI and blood pressure in young children-analyses based on path models. PLoS One. 2017;12:e0181485. https://doi.org/10.1371/journal.pone.0181485

FADS Polymorphisms Affect the Clinical and Biochemical Phenotypes of Metabolic Syndrome