FTO gene

Source: Wikipedia, the free encyclopedia.
(Redirected from Fto gene)
FTO
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesFTO, ALKBH9, GDFD, BMIQ14, fat mass and obesity associated, alpha-ketoglutarate dependent dioxygenase
External IDsOMIM: 610966; MGI: 1347093; HomoloGene: 8053; GeneCards: FTO; OMA:FTO - orthologs
Orthologs
SpeciesHumanMouse
Entrez

79068

26383

Ensembl

ENSG00000140718

ENSMUSG00000055932

UniProt

Q9C0B1

Q8BGW1

RefSeq (mRNA)

NM_001080432

NM_011936

RefSeq (protein)

NP_036066

Location (UCSC)Chr 16: 53.7 – 54.16 MbChr 8: 92.04 – 92.4 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Fat mass and obesity-associated protein also known as alpha-ketoglutarate-dependent dioxygenase FTO is an enzyme that in humans is encoded by the FTO gene located on chromosome 16. As one homolog in the AlkB family proteins, it is the first messenger RNA (mRNA) demethylase that has been identified.[5] Certain alleles of the FTO gene appear to be correlated with obesity in humans.[6][7]

Function

The amino acid sequence of the transcribed FTO protein shows high similarity with the enzyme AlkB which oxidatively demethylates DNA.[8][9] FTO is a member of the superfamily of alpha-ketoglutarate-dependent hydroxylase, which are non-heme iron-containing proteins. Recombinant FTO protein was first discovered to catalyze demethylation of 3-methylthymine in single-stranded DNA, and 3-methyluridine in single-stranded RNA, with low efficiency.[8] The nucleoside N6-methyladenosine (m6A), an abundant modification in RNA, was then found to be a major substrate of FTO.[5][10] The FTO gene expression was also found to be significantly upregulated in the hypothalamus of rats after food deprivation and strongly negatively correlated with the expression of orexigenic galanin-like peptide which is involved in the stimulation of food intake.[11]

Increases in hypothalamic expression of FTO are associated with the regulation of energy intake but not feeding reward.[12]

People with two copies of the risk allele for the rs9939609 single nucleotide polymorphism (SNP) showed differing neural responses to food images via fMRI.[13] However, rs9939609's association with FTO is controversial, and may actually affect another gene, called Iroquois homeobox protein 3 (IRX3).[14]

FTO demethylates RNA

FTO has been demonstrated to efficiently demethylate the related modified ribonucleotide, N6,2'-O-dimethyladenosine, and to an equal or lesser extent, m6A, in vitro .[5][15] FTO knockdown with siRNA led to increased amounts of m6A in polyA-RNA, whereas overexpression of FTO resulted in decreased amounts of m6A in human cells.[10] FTO partially co-localizes with nuclear speckles, which supports the notion that in the nucleus, m6A can be a substrate of FTO. Function of FTO could affect the processing of pre-mRNA, other nuclear RNAs, or both. The discovery of the FTO-mediated oxidative demethylation of RNA may initiate further investigations on biological regulation based on reversible chemical modification of RNA, and identification of RNA substrates for which FTO has the highest affinity.[5][10][15]

FTO can oxidize m6A to generate N6 -hydroxymethyladenosine(hm6A) as an intermediate modification and N6 - formyladenosine(f6A) as a further oxidized product in mammalian cells.[16]

Plants do not carry orthologs of FTO and artificial introduction of an FTO transgene causes substantial and widespread RNA demethylation. Instead of causing catastrophic disregulation, the treated rice and potato plants show significant (50%) increases in yield and become more tolerant to drought.[17] In mESCs and during mouse development, FTO has been shown to mediated LINE1 RNA m6A demethylation and consequently affect local chromatin state and nearby gene transcription.[18]

Tissue distribution

The FTO gene is widely expressed in both fetal and adult tissues.[19]

Clinical significance

Obesity

Fat Mass and Obesity-Associated (FTO) Protein

38,759 Europeans were studied for variants of FTO obesity risk allele.[19] In particular, carriers of one copy of the allele weighed on average 1.2 kilograms (2.6 lb) more than people with no copies. Carriers of two copies (16% of the subjects) weighed 3 kilograms (6.6 lb) more and had a 1.67-fold higher rate of obesity than those with no copies. The association was observed in ages 7 and upwards. This gene is not directly associated with diabetes; however, increased body-fat also increases the risk of developing type 2 diabetes.[20]

Simultaneously, a study of 2,900 affected individuals and 5,100 controls of French descent, together with 500 trios (confirming an association independent of population stratification) found association of SNPs in the very same region of FTO (rs1421085).[21] The authors found that this variation, or a variation in strong LD with this variation explains 1% of the population BMI variance and 22% of the population attributable risk of obesity. The authors of this study claim that while obesity was already known to have a genetic component (from twin studies), no replicated previous study has ever identified an obesity risk allele that was so common in the human population. The risk allele is a cluster of 10 single nucleotide polymorphism in the first intron of FTO called rs9939609. According to HapMap, it has population frequencies of 45% in the West/Central Europeans, 52% in Yorubans (West African natives) and 14% in Chinese/Japanese. Furthermore, morbid obesity is associated with a combination of FTO and INSIG2 single nucleotide polymorphisms.[22]

In 2009, variants in the FTO gene were further confirmed to associate with obesity in two very large genome wide association studies of body mass index (BMI).[23][24]

In adult humans, it was shown that adults bearing the at risk AT and AA alleles at rs9939609 consumed between 500 and 1250 kJ more each day than those carrying the protective TT genotype (equivalent to between 125 and 280 kcal per day more intake).[25] The same study showed that there was no impact of the polymorphism on energy expenditure. This finding of an effect of the rs9939609 polymorphism on food intake or satiety has been independently replicated in five subsequent studies (in order of publication).[26][27][28][29][30] Three of these subsequent studies also measured resting energy expenditure and confirmed the original finding that there is no impact of the polymorphic variation at the rs9939609 locus on energy expenditure. A different study explored the effects of variation in two different SNPs in the FTO gene (rs17817449 and rs1421085) and suggested there might be an effect on circulating leptin levels and energy expenditure, but this latter effect disappeared when the expenditure was normalised for differences in body composition.[31] The accumulated data across seven independent studies therefore clearly implicates the FTO gene in humans as having a direct impact on food intake but no effect on energy expenditure.

Human hypothalamic neurons derived from individuals carrying the obesity-risk variation at FTO SNPs rs1421085 or rs8050136 express lower levels of the adjacent gene RPGRIP1L compared to individuals carrying the protective variation.[32] The transcription factor CUX1 binds DNA at rs1421085 or rs8050136 in the presence of the protective variation and promotes RPGRIP1L expression[33][34] suggesting a potential molecular mechanism by which FTO obesity-associates SNPs alter the expression of nearby genes. Reduced expression of RPGRIP1L in mice results in increased body weight due to increased food intake,[35][36][37] with no changes in energy expenditure, in agreement with data accumulated in human studies. RPGRIP1L is a protein found in primary cilia that are cellular organelles important for body weight regulation. Decreased RPGRIP1L expression in the mouse brain, or cells derived from humans, results in lower sensitivity for the hormone leptin that suppresses feeding, as well as alters the morphology of the hypothalamus that controls food consumption.[32][35][36] These studies provide a potential mechanism by which obesity-risk variations in FTO SNPs promote increased food intake by influencing the function of genes in the vicinity.

The obesity-associated noncoding region within the FTO gene interacts directly with the promoter of IRX3, a homeobox gene, and IRX5, another homeobox gene. The noncoding region of FTO interacts with the promoters of IRX3 and FTO in human, mouse and zebrafish, and with IRX5. Results suggest that IRX3 and IRX5 are linked with obesity and determine body mass and composition. This is further supported by the fact that obesity-associated single nucleotide polymorphisms, in which cytosine is substituted for thymine, are involved in the expression of IRX3 and IRX5 (not FTO) in human brains. The enhanced expression of IRX3 and IRX5 resulting from this single nucleotide alteration promoted a shift from energy-dissipating beige adipocytes to energy-storing white adipocytes and a subsequent reduction in mitochondrial thermogenesis by a factor of 5.[38][39] Another study found indications that the FTO allele associated with obesity represses mitochondrial thermogenesis in adipocyte precursor cells in a tissue-autonomous manner, and that there is a pathway for adipocyte thermoregulation which involves the proteine ARID5B, the single-nucleotide variant rs1421085, and the IRX3 and IRX5 genes.[40]

Alzheimer's disease

Recent studies revealed that carriers of common FTO gene polymorphisms show both a reduction in frontal lobe volume of the brain[41] and an impaired verbal fluency performance.[42] Fittingly, a population-based study from Sweden found that carriers of the FTO rs9939609 A allele have an increased risk for incident Alzheimer disease.[43]

Other diseases

The presence of the FTO rs9939609 A allele was also found to be positively correlated with other symptoms of the metabolic syndrome, including higher fasting insulin, glucose, and triglycerides, and lower HDL cholesterol. However all these effects appear to be secondary to weight increase since no association was found after correcting for increases in body mass index.[44] Similarly, the association of rs11076008 G allele with the increased risk for degenerative disc disease was reported.[45]

Origin of name

By exon trapping, Peters et al. (1999) cloned a novel gene from a region of several hundred kb deleted by the mouse 'fused toes' (FT) mutation. They named the gene 'fatso' (Fto) due to its large size.[46][47]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000140718 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000055932 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b c d Jia G, Fu Y, Zhao X, Dai Q, Zheng G, Yang Y, Yi C, Lindahl T, Pan T, Yang YG, He C (October 2011). "N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO". Nature Chemical Biology. 7 (12): 885–7. doi:10.1038/nchembio.687. PMC 3218240. PMID 22002720.
  6. ^ Loos RJ, Yeo GS (January 2014). "The bigger picture of FTO: the first GWAS-identified obesity gene". Nature Reviews. Endocrinology. 10 (1): 51–61. doi:10.1038/nrendo.2013.227. PMC 4188449. PMID 24247219.
  7. ^ Claussnitzer M, Dankel SN, Kim KH, Quon G, Meuleman W, Haugen C, et al. (September 2015). "FTO Obesity Variant Circuitry and Adipocyte Browning in Humans". The New England Journal of Medicine. 373 (10): 895–907. doi:10.1056/NEJMoa1502214. PMC 4959911. PMID 26287746.
  8. ^ a b Gerken T, Girard CA, Tung YC, Webby CJ, Saudek V, Hewitson KS, Yeo GS, McDonough MA, Cunliffe S, McNeill LA, Galvanovskis J, Rorsman P, Robins P, Prieur X, Coll AP, Ma M, Jovanovic Z, Farooqi IS, Sedgwick B, Barroso I, Lindahl T, Ponting CP, Ashcroft FM, O'Rahilly S, Schofield CJ (November 2007). "The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase". Science. 318 (5855): 1469–72. Bibcode:2007Sci...318.1469G. doi:10.1126/science.1151710. PMC 2668859. PMID 17991826.
  9. ^ Sanchez-Pulido L, Andrade-Navarro MA (November 2007). "The FTO (fat mass and obesity associated) gene codes for a novel member of the non-heme dioxygenase superfamily". BMC Biochemistry. 8: 23. doi:10.1186/1471-2091-8-23. PMC 2241624. PMID 17996046.
  10. ^ a b c Meyer KD, Saletore Y, Zumbo P, Elemento O, Mason CE, Jaffrey SR (June 2012). "Comprehensive analysis of mRNA methylation reveals enrichment in 3' UTRs and near stop codons". Cell. 149 (7): 1635–46. doi:10.1016/j.cell.2012.05.003. PMC 3383396. PMID 22608085.
  11. ^ Fredriksson R, Hägglund M, Olszewski PK, Stephansson O, Jacobsson JA, Olszewska AM, Levine AS, Lindblom J, Schiöth HB (May 2008). "The obesity gene, FTO, is of ancient origin, up-regulated during food deprivation and expressed in neurons of feeding-related nuclei of the brain". Endocrinology. 149 (5): 2062–71. doi:10.1210/en.2007-1457. PMID 18218688.
  12. ^ Olszewski PK, Fredriksson R, Olszewska AM, Stephansson O, Alsiö J, Radomska KJ, Levine AS, Schiöth HB (October 2009). "Hypothalamic FTO is associated with the regulation of energy intake not feeding reward". BMC Neuroscience. 10: 129. doi:10.1186/1471-2202-10-129. PMC 2774323. PMID 19860904.
  13. ^ Wiemerslage L, Nilsson EK, Solstrand Dahlberg L, Ence-Eriksson F, Castillo S, Larsen AL, Bylund SB, Hogenkamp PS, Olivo G, Bandstein M, Titova OE, Larsson EM, Benedict C, Brooks SJ, Schiöth HB (May 2016). "An obesity-associated risk allele within the FTO gene affects human brain activity for areas important for emotion, impulse control and reward in response to food images" (PDF). The European Journal of Neuroscience. 43 (9): 1173–80. doi:10.1111/ejn.13177. PMID 26797854. S2CID 4538964.
  14. ^ Rask-Andersen M, Almén MS, Schiöth HB (November 2015). "Scrutinizing the FTO locus: compelling evidence for a complex, long-range regulatory context". Human Genetics. 134 (11–12): 1183–93. doi:10.1007/s00439-015-1599-5. PMID 26340902. S2CID 16199296.
  15. ^ a b Mauer J, Luo X, Blanjoie A, Jiao X, Grozhik AV, Patil DP, Linder B, Pickering BF, Vasseur JJ, Chen Q, Gross SS, Elemento O, Debart F, Kiledjian M, Jaffrey SR (January 2017). "Reversible methylation of m6Am in the 5' cap controls mRNA stability". Nature. 541 (7637): 371–375. Bibcode:2017Natur.541..371M. doi:10.1038/nature21022. PMC 5513158. PMID 28002401.
  16. ^ Fu Y, Jia G, Pang X, Wang RN, Wang X, Li CJ, et al. (2013). "FTO-mediated formation of N6-hydroxymethyladenosine and N6-formyladenosine in mammalian RNA". Nature Communications. 4: 1798. Bibcode:2013NatCo...4.1798F. doi:10.1038/ncomms2822. PMC 3658177. PMID 23653210.
  17. ^ Yu Q, Liu S, Yu L, Xiao Y, Zhang S, Wang X, et al. (July 2021). "RNA demethylation increases the yield and biomass of rice and potato plants in field trials". Nature Biotechnology. 39 (12): 1581–1588. doi:10.1038/s41587-021-00982-9. PMID 34294912. S2CID 236197910.*Lay summary in: Kim SE (August 17, 2021). "Researchers Transfer a Human Protein Into Plants to Supersize Them". Smithsonian Magazine.
  18. ^ Wei, Jiangbo; Yu, Xianbin; Yang, Lei; Liu, Xuelian; Gao, Boyang; Huang, Boxian; Dou, Xiaoyang; Liu, Jun; Zou, Zhongyu; Cui, Xiao-Long; Zhang, Li-Sheng; Zhao, Xingsen; Liu, Qinzhe; He, P. Cody; Sepich-Poore, Caraline (2022-05-27). "FTO mediates LINE1 m6A demethylation and chromatin regulation in mESCs and mouse development". Science. 376 (6596): 968–973. Bibcode:2022Sci...376..968W. doi:10.1126/science.abe9582. ISSN 1095-9203. PMC 9746489. PMID 35511947.
  19. ^ a b Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, et al. (May 2007). "A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity". Science. 316 (5826): 889–94. Bibcode:2007Sci...316..889F. doi:10.1126/science.1141634. PMC 2646098. PMID 17434869.
  20. ^ Sandholt CH, Hansen T, Pedersen O (July 2012). "Beyond the fourth wave of genome-wide obesity association studies". Nutrition & Diabetes. 2 (7): e37. doi:10.1038/nutd.2012.9. PMC 3408643. PMID 23168490.
  21. ^ Dina C, Meyre D, Gallina S, Durand E, Körner A, Jacobson P, Carlsson LM, Kiess W, Vatin V, Lecoeur C, Delplanque J, Vaillant E, Pattou F, Ruiz J, Weill J, Levy-Marchal C, Horber F, Potoczna N, Hercberg S, Le Stunff C, Bougnères P, Kovacs P, Marre M, Balkau B, Cauchi S, Chèvre JC, Froguel P (June 2007). "Variation in FTO contributes to childhood obesity and severe adult obesity". Nature Genetics. 39 (6): 724–6. doi:10.1038/ng2048. PMID 17496892. S2CID 3248168.
  22. ^ Chu X, Erdman R, Susek M, Gerst H, Derr K, Al-Agha M, Wood GC, Hartman C, Yeager S, Blosky MA, Krum W, Stewart WF, Carey D, Benotti P, Still CD, Gerhard GS (March 2008). "Association of morbid obesity with FTO and INSIG2 allelic variants". Archives of Surgery. 143 (3): 235–40, discussion 241. doi:10.1001/archsurg.2007.77. PMID 18347269.
  23. ^ Thorleifsson G, Walters GB, Gudbjartsson DF, Steinthorsdottir V, Sulem P, Helgadottir A, Styrkarsdottir U, Gretarsdottir S, Thorlacius S, Jonsdottir I, Jonsdottir T, Olafsdottir EJ, Olafsdottir GH, Jonsson T, Jonsson F, Borch-Johnsen K, Hansen T, Andersen G, Jorgensen T, Lauritzen T, Aben KK, Verbeek AL, Roeleveld N, Kampman E, Yanek LR, Becker LC, Tryggvadottir L, Rafnar T, Becker DM, Gulcher J, Kiemeney LA, Pedersen O, Kong A, Thorsteinsdottir U, Stefansson K (January 2009). "Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity". Nature Genetics. 41 (1): 18–24. doi:10.1038/ng.274. PMID 19079260. S2CID 764409.
  24. ^ Willer CJ, Speliotes EK, Loos RJ, Li S, Lindgren CM, Heid IM, et al. (January 2009). "Six new loci associated with body mass index highlight a neuronal influence on body weight regulation". Nature Genetics. 41 (1): 25–34. doi:10.1038/ng.287. PMC 2695662. PMID 19079261.
  25. ^ Speakman JR, Rance KA, Johnstone AM (August 2008). "Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure". Obesity. 16 (8): 1961–5. doi:10.1038/oby.2008.318. PMID 18551109. S2CID 33151950.
  26. ^ Wardle J, Carnell S, Haworth CM, Farooqi IS, O'Rahilly S, Plomin R (September 2008). "Obesity associated genetic variation in FTO is associated with diminished satiety". The Journal of Clinical Endocrinology and Metabolism. 93 (9): 3640–3. doi:10.1210/jc.2008-0472. PMID 18583465.
  27. ^ Timpson NJ, Emmett PM, Frayling TM, Rogers I, Hattersley AT, McCarthy MI, Davey Smith G (October 2008). "The fat mass- and obesity-associated locus and dietary intake in children". The American Journal of Clinical Nutrition. 88 (4): 971–8. doi:10.1093/ajcn/88.4.971. PMC 4773885. PMID 18842783.
  28. ^ Haupt A, Thamer C, Staiger H, Tschritter O, Kirchhoff K, Machicao F, Häring HU, Stefan N, Fritsche A (April 2009). "Variation in the FTO gene influences food intake but not energy expenditure". Experimental and Clinical Endocrinology & Diabetes. 117 (4): 194–7. doi:10.1055/s-0028-1087176. PMID 19053021.
  29. ^ Wardle J, Llewellyn C, Sanderson S, Plomin R (January 2009). "The FTO gene and measured food intake in children". International Journal of Obesity. 33 (1): 42–5. doi:10.1038/ijo.2008.174. PMID 18838977.
  30. ^ Cecil JE, Tavendale R, Watt P, Hetherington MM, Palmer CN (December 2008). "An obesity-associated FTO gene variant and increased energy intake in children". The New England Journal of Medicine. 359 (24): 2558–66. doi:10.1056/NEJMoa0803839. PMID 19073975.
  31. ^ Do R, Bailey SD, Desbiens K, Belisle A, Montpetit A, Bouchard C, Pérusse L, Vohl MC, Engert JC (April 2008). "Genetic variants of FTO influence adiposity, insulin sensitivity, leptin levels, and resting metabolic rate in the Quebec Family Study". Diabetes. 57 (4): 1147–50. doi:10.2337/db07-1267. PMID 18316358.
  32. ^ a b Wang L, De Solis AJ, Goffer Y, Birkenbach KE, Engle SE, Tanis R, et al. (February 2019). "Ciliary gene RPGRIP1L is required for hypothalamic arcuate neuron development". JCI Insight. 4 (3). doi:10.1172/jci.insight.123337. PMC 6413800. PMID 30728336.
  33. ^ Stratigopoulos G, LeDuc CA, Cremona ML, Chung WK, Leibel RL (January 2011). "Cut-like homeobox 1 (CUX1) regulates expression of the fat mass and obesity-associated and retinitis pigmentosa GTPase regulator-interacting protein-1-like (RPGRIP1L) genes and coordinates leptin receptor signaling". The Journal of Biological Chemistry. 286 (3): 2155–70. doi:10.1074/jbc.m110.188482. PMC 3023512. PMID 21037323.
  34. ^ Stratigopoulos G, Padilla SL, LeDuc CA, Watson E, Hattersley AT, McCarthy MI, et al. (April 2008). "Regulation of Fto/Ftm gene expression in mice and humans". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 294 (4): R1185-96. doi:10.1152/ajpregu.00839.2007. PMC 2808712. PMID 18256137.
  35. ^ a b Stratigopoulos G, Martin Carli JF, O'Day DR, Wang L, Leduc CA, Lanzano P, et al. (May 2014). "Hypomorphism for RPGRIP1L, a ciliary gene vicinal to the FTO locus, causes increased adiposity in mice". Cell Metabolism. 19 (5): 767–79. doi:10.1016/j.cmet.2014.04.009. PMC 4131684. PMID 24807221.
  36. ^ a b Stratigopoulos G, Burnett LC, Rausch R, Gill R, Penn DB, Skowronski AA, et al. (May 2016). "Hypomorphism of Fto and Rpgrip1l causes obesity in mice". The Journal of Clinical Investigation. 126 (5): 1897–910. doi:10.1172/JCI85526. PMC 4855930. PMID 27064284.
  37. ^ Lewis WR, Bales KL, Revell DZ, Croyle MJ, Engle SE, Song CJ, et al. (January 2019). "Mks6 mutations reveal tissue- and cell type-specific roles for the cilia transition zone". FASEB Journal. 33 (1): 1440–1455. doi:10.1096/fj.201801149R. PMC 6355093. PMID 30133325.
  38. ^ Smemo S, Tena JJ, Kim KH, Gamazon ER, Sakabe NJ, Gómez-Marín C, Aneas I, Credidio FL, Sobreira DR, Wasserman NF, Lee JH, Puviindran V, Tam D, Shen M, Son JE, Vakili NA, Sung HK, Naranjo S, Acemel RD, Manzanares M, Nagy A, Cox NJ, Hui CC, Gomez-Skarmeta JL, Nóbrega MA (March 2014). "Obesity-associated variants within FTO form long-range functional connections with IRX3". Nature. 507 (7492): 371–5. Bibcode:2014Natur.507..371S. doi:10.1038/nature13138. PMC 4113484. PMID 24646999.
  39. ^ Harrison P (19 August 2015). "Obesity Genetics: New Insights Might Mean New Therapies". Medscape.
  40. ^ Claussnitzer M, Dankel SN, Kim KH, Quon G, Meuleman W, Haugen C, Glunk V, Sousa IS, Beaudry JL, Puviindran V, Abdennur NA, Liu J, Svensson PA, Hsu YH, Drucker DJ, Mellgren G, Hui CC, Hauner H, Kellis M (September 2015). "FTO Obesity Variant Circuitry and Adipocyte Browning in Humans". The New England Journal of Medicine. 373 (10): 895–907. doi:10.1056/NEJMoa1502214. PMC 4959911. PMID 26287746.
  41. ^ Ho AJ, Stein JL, Hua X, Lee S, Hibar DP, Leow AD, et al. (May 2010). "A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly". Proceedings of the National Academy of Sciences of the United States of America. 107 (18): 8404–9. Bibcode:2010PNAS..107.8404H. doi:10.1073/pnas.0910878107. PMC 2889537. PMID 20404173.
  42. ^ Benedict C, Jacobsson JA, Rönnemaa E, Sällman-Almén M, Brooks S, Schultes B, Fredriksson R, Lannfelt L, Kilander L, Schiöth HB (June 2011). "The fat mass and obesity gene is linked to reduced verbal fluency in overweight and obese elderly men". Neurobiology of Aging. 32 (6): 1159.e1–5. doi:10.1016/j.neurobiolaging.2011.02.006. PMID 21458110. S2CID 20051507.
  43. ^ Keller L, Xu W, Wang HX, Winblad B, Fratiglioni L, Graff C (2011). "The obesity related gene, FTO, interacts with APOE, and is associated with Alzheimer's disease risk: a prospective cohort study". Journal of Alzheimer's Disease. 23 (3): 461–9. doi:10.3233/JAD-2010-101068. PMID 21098976.
  44. ^ Freathy RM, Timpson NJ, Lawlor DA, Pouta A, Ben-Shlomo Y, Ruokonen A, Ebrahim S, Shields B, Zeggini E, Weedon MN, Lindgren CM, Lango H, Melzer D, Ferrucci L, Paolisso G, Neville MJ, Karpe F, Palmer CN, Morris AD, Elliott P, Jarvelin MR, Smith GD, McCarthy MI, Hattersley AT, Frayling TM (May 2008). "Common variation in the FTO gene alters diabetes-related metabolic traits to the extent expected given its effect on BMI". Diabetes. 57 (5): 1419–26. doi:10.2337/db07-1466. PMC 3073395. PMID 18346983.
  45. ^ Lao L, Zhong G, Li X, Liu Z (February 2014). "A preliminary association study of fat mass and obesity associated gene polymorphisms and degenerative disc disease in a Chinese Han population". The Journal of International Medical Research. 42 (1): 205–12. doi:10.1177/0300060513503761. PMID 24304927.
  46. ^ Peters T, Ausmeier K, Rüther U (October 1999). "Cloning of Fatso (Fto), a novel gene deleted by the Fused toes (Ft) mouse mutation". Mammalian Genome. 10 (10): 983–6. doi:10.1007/s003359901144. PMID 10501967. S2CID 20362657.
  47. ^ Kim B, Kim Y, Cooke PS, Rüther U, Jorgensen JS (May 2011). "The fused toes locus is essential for somatic-germ cell interactions that foster germ cell maturation in developing gonads in mice". Biology of Reproduction. 84 (5): 1024–32. doi:10.1095/biolreprod.110.088559. PMID 21293032.
Retrieved from "https://en.wikipedia.org/w/index.php?title=FTO_gene&oldid=1227802700"