Biology:FADS2
 Generic protein structure example |
Fatty acid desaturase 2 (FADS2) is an enzyme that in humans is encoded by the FADS2 gene.[1][2]
Function
The protein encoded by the FADS2 gene is a member of the fatty acid desaturase (FADS) gene family and desaturates omega-3 and omega-6 polyunsaturated fatty acids at the delta-6 position, catalyzing the first and rate-limiting step in the formation of tetracosapentaenoic acid and tetracosahexaenoic acid. Despite the name, it was also shown to catalyze some delta-8 and delta-4 desaturation reactions.[3] Desaturase enzymes (such as those encoded by FADS2) cause desaturation of fatty acids through the introduction of double bonds between defined carbons of the fatty acyl chain. FADS family members are considered fusion products composed of an N-terminal cytochrome b5-like domain and a C-terminal multiple membrane-spanning desaturase portion, both of which are characterized by conserved histidine motifs. This gene is clustered with family members FADS1 and FADS2 at 11q12-q13.1; this cluster is thought to have arisen evolutionarily from gene duplication based on its similar exon/intron organization.[1]
Clinical significance
It was reported the FADS2 interacts with breastfeeding such that breast-fed children with the "C" version of the gene appear about 7 intelligence quotient (IQ) points higher than those with the less common "G" version (less than this when adjusted for maternal IQ).[4][5]
An attempt to replicate this study in 5934 8-year-old children failed: No relationship of the common C allele to negative effects of formula feeding was apparent, and contra to the original report, the rare GG homozygote children performed worse when formula fed than other children on formula milk.[6] A study of over 700 families recently found no evidence for either main or moderating effects of the original SNP (rs174575), nor of two additional FADS2 polymorphisms (rs1535 and rs174583), nor any effect of maternal FADS2 status on offspring IQ.[7]
References
- ↑ 1.0 1.1 "Entrez Gene: FADS1 fatty acid desaturase 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3992.
- ↑ "cDNA cloning, genomic structure, and chromosomal localization of three members of the human fatty acid desaturase family". Genomics 66 (2): 175–83. June 2000. doi:10.1006/geno.2000.6196. PMID 10860662.
- ↑ Brenna, J Thomas (June 2009). "An alternate pathway to long-chain polyunsaturates: the FADS2 gene product Δ8-desaturates 20:2n-6 and 20:3n-3". Journal of Lipid Research 50 (6): 1195–202. doi:10.1194/jlr.M800630-JLR200. PMID 19202133.
- ↑ Gene governs IQ boost from breastfeeding.
- ↑ "Moderation of breastfeeding effects on the IQ by genetic variation in fatty acid metabolism". Proc. Natl. Acad. Sci. U.S.A. 104 (47): 18860–5. November 2007. doi:10.1073/pnas.0704292104. PMID 17984066. Bibcode: 2007PNAS..10418860C.
- ↑ "FADS2 polymorphisms modify the effect of breastfeeding on child IQ". PLOS ONE 5 (7): e11570. 2010. doi:10.1371/journal.pone.0011570. PMID 20644632. Bibcode: 2010PLoSO...511570S.
- ↑ "Cognitive function in adolescence: testing for interactions between breast-feeding and FADS2 polymorphisms". J Am Acad Child Adolesc Psychiatry 50 (1): 55–62.e4. January 2011. doi:10.1016/j.jaac.2010.10.010. PMID 21156270.
Further reading
- "A genome-wide association study of the metabolic syndrome in Indian Asian men.". PLOS ONE 5 (8): e11961. 2010. doi:10.1371/journal.pone.0011961. PMID 20694148. Bibcode: 2010PLoSO...511961Z.
- "Genetic variants of the FADS1 FADS2 gene cluster as related to essential fatty acid metabolism.". Curr. Opin. Lipidol. 21 (1): 64–9. 2010. doi:10.1097/MOL.0b013e3283327ca8. PMID 19809313.
- "Association of fatty acid desaturase gene polymorphisms with blood lipid essential fatty acids and perinatal depression among Canadian women: a pilot study.". J. Nutr. Nutr. 2 (4–5): 243–50. 2009. doi:10.1159/000255636. PMID 20395685.
- "FADS gene polymorphisms in Koreans: association with ω6 polyunsaturated fatty acids in serum phospholipids, lipid peroxides, and coronary artery disease.". Atherosclerosis 214 (1): 94–100. 2011. doi:10.1016/j.atherosclerosis.2010.10.004. PMID 21040914.
- "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 5 (10): e13261. 2010. doi:10.1371/journal.pone.0013261. PMID 20948998. Bibcode: 2010PLoSO...513261R.
- "FADS gene cluster polymorphisms: important modulators of fatty acid levels and their impact on atopic diseases.". J. Nutr. Nutr. 2 (3): 119–28. 2009. doi:10.1159/000235559. PMID 19776639. https://epub.ub.uni-muenchen.de/16661/1/10_1159_000235559.pdf.
- "Do FADS genotypes enhance our knowledge about fatty acid related phenotypes?". Clin Nutr 29 (3): 277–87. 2010. doi:10.1016/j.clnu.2009.11.005. PMID 19948371.
- "FADS genetic variants and omega-6 polyunsaturated fatty acid metabolism in a homogeneous island population.". J. Lipid Res. 51 (9): 2766–74. 2010. doi:10.1194/jlr.M008359. PMID 20562440.
- "Genetic variants of the fatty acid desaturase gene cluster predict amounts of red blood cell docosahexaenoic and other polyunsaturated fatty acids in pregnant women: findings from the Avon Longitudinal Study of Parents and Children.". Am. J. Clin. Nutr. 93 (1): 211–9. 2011. doi:10.3945/ajcn.110.006189. PMID 21106917.
- "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. 51 (8): 2325–33. 2010. doi:10.1194/jlr.M006205. PMID 20427696.
- "Role of FADS1 and FADS2 polymorphisms in polyunsaturated fatty acid metabolism.". Metab. Clin. Exp. 59 (7): 993–9. 2010. doi:10.1016/j.metabol.2009.10.022. PMID 20045144.
- "FADS2 polymorphisms modify the effect of breastfeeding on child IQ.". PLOS ONE 5 (7): e11570. 2010. doi:10.1371/journal.pone.0011570. PMID 20644632. Bibcode: 2010PLoSO...511570S.
- "Genetic variation in lipid desaturases and its impact on the development of human disease.". Lipids Health Dis 9: 63. 2010. doi:10.1186/1476-511X-9-63. PMID 20565855.
- "Erythrocyte membrane phospholipid fatty acids, desaturase activity, and dietary fatty acids in relation to risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study.". Am. J. Clin. Nutr. 93 (1): 127–42. 2011. doi:10.3945/ajcn.110.005447. PMID 20980488.
- Genetically determined variation in polyunsaturated fatty acid metabolism may result in different dietary requirements.. Nestlé Nutrition Workshop Series: Pediatric Program. 62. 2008. pp. 35–44; discussion 44–49. doi:10.1159/000146246. ISBN 978-3-8055-8553-8. http://nbn-resolving.de/urn:nbn:de:bvb:19-epub-35257-7.
- Segrè AV (2010). "Common inherited variation in mitochondrial genes is not enriched for associations with type 2 diabetes or related glycemic traits.". PLOS Genet. 6 (8): e1001058. doi:10.1371/journal.pgen.1001058. PMID 20714348.
- "Genetic variation of the FADS1 FADS2 gene cluster and n-6 PUFA composition in erythrocyte membranes in the European Prospective Investigation into Cancer and Nutrition-Potsdam study". Br. J. Nutr. 104 (12): 1748–59. December 2010. doi:10.1017/S0007114510002916. PMID 20691134.
- "Genetic loci associated with lipid concentrations and cardiovascular risk factors in the Korean population.". J. Med. Genet. 48 (1): 10–5. 2011. doi:10.1136/jmg.2010.081000. PMID 20972250.
- "Dietary n-3 and n-6 polyunsaturated fatty acid intake interacts with FADS1 genetic variation to affect total and HDL-cholesterol concentrations in the Doetinchem Cohort Study". Am. J. Clin. Nutr. 92 (1): 258–65. July 2010. doi:10.3945/ajcn.2009.29130. PMID 20484448.
- "Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.". Diabetes Care 33 (10): 2250–3. 2010. doi:10.2337/dc10-0452. PMID 20628086.
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