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FGA  -  fibrinogen alpha chain

Homo sapiens

 
 
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Disease relevance of FGA

 

Psychiatry related information on FGA

  • The short tandem repeats (STR) D3S1358, VWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820 and a locus allowing sex discrimination (amelogenin) can be coamplified by the polymerase chain reaction using a commercially available kit, and subsequently typed using capillary electrophoresis [5].
  • Specific predictors of HRQL efficacy included self-efficacy for OL, negative and positive symptoms for RP, dysphoric mood and positive symptoms, daily doses and self-efficacy for FGA treated patients [6].
  • BACKGROUND: Second generation antipsychotics (SGA) have demonstrated several advantages over first generation antipsychotics (FGA) in terms of positive, negative, cognitive, and affective symptoms and a lower propensity for extrapyramidal side effects [7].
 

High impact information on FGA

  • The amino acid sequence of the human fibrinogen alpha-chain reveals a structure that can be divided into three zones of unique amino acid composition [8].
  • Haplotype data suggest that these deletions occurred separately, on three distinct ancestral chromosomes, implying that the FGA region of the fibrinogen locus is susceptible to deletion by a common mechanism [9].
  • We found no evidence that the haloperidol dose (or all FGA comparators converted to haloperidol-equivalent doses) affected these results when we examined its effect by drug or in a 2-way analysis of variance model in which SGA effectiveness is entered as a second factor [10].
  • The message for a second fibrinogen alpha chain has been cloned from a lamprey liver cDNA library [11].
  • Outcome of donor splice site mutations accounting for congenital afibrinogenemia reflects order of intron removal in the fibrinogen alpha gene (FGA) [12].
 

Biological context of FGA

  • Molecular analysis of the fibrinogen gene cluster in 16 patients with congenital afibrinogenemia: novel truncating mutations in the FGA and FGG genes [13].
  • All are due to mutations in one of the three fibrinogen genes, FGA, FGB and FGG, which are clustered in a region of 50 kb on the long arm of human chromosome 4 [14].
  • Two regions of the fibrinogen alpha chain that contain an RGD motif, as well as the carboxyl-terminus of the fibrinogen gamma chain, represent potential binding sites for GPIIb-IIIa in the fibrinogen molecule [15].
  • The FGG-FGA*4 haplotype, composed of the minor FGG 9340C and FGA 2224A alleles, had similar effects, supporting its reported protective role in relation to MI [16].
  • Significant epistasis on plasma fibrinogen concentration was detected between the FGA 2224G > A and F13A1 Val34Leu [rs5985] SNPs (p < 0.001) [16].
 

Anatomical context of FGA

  • Our results confirm the utility of transfecting COS-7 cells to study mRNA splice-site mutations and demonstrate that the common FGA IVS4 variant is a null mutation leading to afibrinogenemia [17].
  • Human isolates of dengue (DEN) type 1 viruses FGA/89 and BR/90 differ in their membrane fusion properties in mosquito cell lines (P. Desprès et al., Virology 196:209-216, 1993) [18].
  • FGA/89 and BR/90 were assayed for their neurovirulence in newborn mice, and neurons were the major target cells for both DEN-1 virus strains within the central nervous system [18].
  • Infection of mosquito cell lines with BR/90 virus strain induced a cytopathic effect characterized by syncytium formation whereas no cytopathic changes were observed with FGA/89 [19].
  • We investigated these issues in patient FGA who had intracerebral electrodes stereotaxically implanted in the right temporal lobe for investigation of drug-resistant epilepsy [20].
 

Associations of FGA with chemical compounds

  • A homozygous C --> T mutation was found at nucleotide 3108 in exon 4 of the FGA gene of the proposita and her father; it is a null mutation predicting to produce severely truncated A alpha-chains because of the presence of premature termination at the Gln 150 codon (or truncated at the 131 residues according to the mature A alpha-chain) [21].
  • A carboxyl-terminal decapeptide of the fibrinogen gamma-chain (Leu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val LGGAKQAGDV] and a tetrapeptide (Arg-Gly-Asp-Ser (RGDS] from the fibrinogen alpha-chain and the fibronectin cell-binding domain appear to mediate the binding of these ligands to GP IIb-IIIa [22].
  • In this study the biological activities of SC-46749 were examined and its actions compared with the tetrapeptide arginine-glycine-aspartic acid-serine (RGDS), one of the natural sequences on the fibrinogen alpha chain that binds to platelets [23].
  • CONCLUSIONS: Volumetric increase of cerebral cortical gray occurred early in the course of treatment with the SGAs ziprasidone and risperidone, but not with the FGA haloperidol [24].
  • TOGE-2 treatment clearly activates resistance against both pathogens and improves the protective effect previously shown by FGA mixture (adipic acid monoethyl ester, 1,2,3,4-tetra-O-acetyl-beta- D-glucopyranose and furfurylamine) [V. Flors et al. (2001) J Agric Food Chem 49:2569-2575] [25].
 

Physical interactions of FGA

  • These results suggested that the tyrosine sulfation site in 3Y1 secreted fibronectin is located in the C-terminal fibrin-binding (Fib-2) domain, being within 17 kDa of the C-terminus [26].
 

Other interactions of FGA

  • Coexpression of the FGB G444S mutant cDNA in combination with wild-type FGA and FGG cDNAs demonstrated that fibrinogen molecules containing the mutant beta chain are able to assemble but are not secreted into the media, confirming the pathogenic nature of the identified mutation [1].
  • In contrast, in male controls the FGA 2224G>A htSNP was significantly associated with serum IL-6 concentration (P < 0.05) [27].
  • CONCLUSION: Though the FGA and UCP1 markers showed nearly significant p values for linkage and association, respectively, the results of the present study provided insufficient evidence of the existence of a major susceptibility locus in the 4q region that was analyzed in the present study [28].
  • Approximately 12,000 meiotic transfers were investigated and 19 mutations were observed in the repeat units of FGA (n=6), ACTBP2 (n=5), D3S1358 (n=2), D5S818 (n=2), D7S820 (n=2), VWA (n=1) and D8S1179 (n=1) [29].
  • Tetrapeptide, RGDS, analogous to human fibrinogen alpha chain (alpha 572-575) and to the cell adhesion site of fibronectin, also inhibited aggregation induced by mutant Re595 (IC50 60 mumol/L) [30].
 

Analytical, diagnostic and therapeutic context of FGA

  • Donors' and recipients' DNA was amplified with fluorescent PCR primers specific for short tandem repeat (STR) marker loci: FGA, VWA, TH01, F13A1, D21S11 [31].
  • In European-Americans, a common haplotype tagged by FGA Thr312Ala and several other variant alleles across the fibrinogen gene locus was strongly associated with decreased fibrinogen levels as measured by functional assay, but not by immunoassay [32].
  • We performed (1) a meta-analysis of randomized efficacy trials comparing SGAs and FGAs, (2) comparisons between SGAs, (3) a dose-response analysis of FGAs and SGAs, and (4) an analysis of the effect on efficacy of an overly high dose of an FGA comparator [10].
  • DEN-1 virus strains BR/90 and FGA/89 were selected on the basis of their membrane fusion properties in mosquito cell cultures [19].
  • Report of the European DNA profiling group (EDNAP): an investigation of the complex STR loci D21S11 and HUMFIBRA (FGA) [33].

References

  1. Congenital afibrinogenemia: identification and expression of a missense mutation in FGB impairing fibrinogen secretion. Vu, D., Bolton-Maggs, P.H., Parr, J.R., Morris, M.A., de Moerloose, P., Neerman-Arbez, M. Blood (2003) [Pubmed]
  2. Hereditary renal amyloidosis associated with a mutant fibrinogen alpha-chain. Benson, M.D., Liepnieks, J., Uemichi, T., Wheeler, G., Correa, R. Nat. Genet. (1993) [Pubmed]
  3. Genetic variation in the fibrinogen gamma gene increases the risk for deep venous thrombosis by reducing plasma fibrinogen gamma' levels. Uitte de Willige, S., de Visser, M.C., Houwing-Duistermaat, J.J., Rosendaal, F.R., Vos, H.L., Bertina, R.M. Blood (2005) [Pubmed]
  4. Fibrinogen gene haplotypes in relation to risk of coronary events and coronary and extracoronary atherosclerosis: The Rotterdam Study. Kardys, I., Uitterlinden, A.G., Hofman, A., Witteman, J.C., de Maat, M.P. Thromb. Haemost. (2007) [Pubmed]
  5. Population genetic studies on nine tetrameric short tandem repeat loci using fluorescence dye-labeled primers and capillary electrophoresis in the Austrian population. Klintschar, M., Ebner, A., Reichenpfader, B. Electrophoresis (1999) [Pubmed]
  6. The effectiveness and predictors of response to antipsychotic agents to treat impaired quality of life in schizophrenia: A 12-month naturalistic follow-up study with implications for confounding factors, antidepressants, anxiolytics, and mood stabilizers. Ritsner, M.S., Gibel, A. Prog. Neuropsychopharmacol. Biol. Psychiatry (2006) [Pubmed]
  7. Metabolic risk factor profile associated with use of second generation antipsychotics: a cross sectional study in a Community Mental Health Centre. Tarricone, I., Casoria, M., Gozzi, B.F., Grieco, D., Menchetti, M., Serretti, A., Ujkaj, M., Pastorelli, F., Berardi, D. BMC psychiatry [electronic resource]. (2006) [Pubmed]
  8. The amino acid sequence of the alpha-chain of human fibrinogen. Doolittle, R.F., Watt, K.W., Cottrell, B.A., Strong, D.D., Riley, M. Nature (1979) [Pubmed]
  9. Deletion of the fibrinogen [correction of fibrogen] alpha-chain gene (FGA) causes congenital afibrogenemia. Neerman-Arbez, M., Honsberger, A., Antonarakis, S.E., Morris, M.A. J. Clin. Invest. (1999) [Pubmed]
  10. A meta-analysis of the efficacy of second-generation antipsychotics. Davis, J.M., Chen, N., Glick, I.D. Arch. Gen. Psychiatry (2003) [Pubmed]
  11. cDNA sequence of a second fibrinogen alpha chain in lamprey: an archetypal version alignable with full-length beta and gamma chains. Pan, Y., Doolittle, R.F. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  12. Outcome of donor splice site mutations accounting for congenital afibrinogenemia reflects order of intron removal in the fibrinogen alpha gene (FGA). Attanasio, C., David, A., Neerman-Arbez, M. Blood (2003) [Pubmed]
  13. Molecular analysis of the fibrinogen gene cluster in 16 patients with congenital afibrinogenemia: novel truncating mutations in the FGA and FGG genes. Neerman-Arbez, M., de Moerloose, P., Honsberger, A., Parlier, G., Arnuti, B., Biron, C., Borg, J.Y., Eber, S., Meili, E., Peter-Salonen, K., Ripoll, L., Vervel, C., d'Oiron, R., Staeger, P., Antonarakis, S.E., Morris, M.A. Hum. Genet. (2001) [Pubmed]
  14. Molecular basis of fibrinogen deficiency. Neerman-Arbez, M. Pathophysiol. Haemost. Thromb. (2006) [Pubmed]
  15. Platelet-fibrinogen interactions. Bennett, J.S. Ann. N. Y. Acad. Sci. (2001) [Pubmed]
  16. Epistatic and pleiotropic effects of polymorphisms in the fibrinogen and coagulation factor XIII genes on plasma fibrinogen concentration, fibrin gel structure and risk of myocardial infarction. Mannila, M.N., Eriksson, P., Ericsson, C.G., Hamsten, A., Silveira, A. Thromb. Haemost. (2006) [Pubmed]
  17. Activation of multiple cryptic donor splice sites by the common congenital afibrinogenemia mutation, FGA IVS4 + 1 G-->T. Attanasio, C., de Moerloose, P., Antonarakis, S.E., Morris, M.A., Neerman-Arbez, M. Blood (2001) [Pubmed]
  18. Human isolates of dengue type 1 virus induce apoptosis in mouse neuroblastoma cells. Desprès, P., Flamand, M., Ceccaldi, P.E., Deubel, V. J. Virol. (1996) [Pubmed]
  19. Differences between cell membrane fusion activities of two dengue type-1 isolates reflect modifications of viral structure. Desprès, P., Frenkiel, M.P., Deubel, V. Virology (1993) [Pubmed]
  20. Recollection of vivid memories after perirhinal region stimulations: synchronization in the theta range of spatially distributed brain areas. Barbeau, E., Wendling, F., Régis, J., Duncan, R., Poncet, M., Chauvel, P., Bartolomei, F. Neuropsychologia. (2005) [Pubmed]
  21. A novel nonsense mutation in the FGA gene in a Chinese family with congenital afibrinogenaemia. Wu, S., Wang, Z., Dong, N., Bai, X., Ruan, C. Blood Coagul. Fibrinolysis (2005) [Pubmed]
  22. Synthetic peptides derived from fibrinogen and fibronectin change the conformation of purified platelet glycoprotein IIb-IIIa. Parise, L.V., Helgerson, S.L., Steiner, B., Nannizzi, L., Phillips, D.R. J. Biol. Chem. (1987) [Pubmed]
  23. Antiplatelet and antithrombotic effects of platelet glycoprotein IIb/IIIa (GPIIb/IIIa) inhibition by arginine-glycine-aspartic acid-serine (RGDS) and arginine-glycine-aspartic acid (RGD) (O-me)Y (SC-46749). Nicholson, N.S., Panzer-Knodle, S.G., Salyers, A.K., Taite, B.B., King, L.W., Miyano, M., Gorczynski, R.J., Williams, M.H., Zupec, M.E., Tjoeng, F.S. J. Pharmacol. Exp. Ther. (1991) [Pubmed]
  24. Cerebral cortical gray expansion associated with two second-generation antipsychotics. Garver, D.L., Holcomb, J.A., Christensen, J.D. Biol. Psychiatry (2005) [Pubmed]
  25. Induction of protection against the necrotrophic pathogens Phytophthora citrophthora and Alternaria solani in Lycopersicon esculentum Mill. by a novel synthetic glycoside combined with amines. Flors, V., Miralles, M.C., González-Bosch, C., Carda, M., García-Agustín, P. Planta (2003) [Pubmed]
  26. Tyrosine sulfation site is located in the C-terminal fibrin-binding domain in secreted fibronectin from rat embryo fibroblasts, line 3Y1. Liu, M.C., Suiko, M. Arch. Biochem. Biophys. (1987) [Pubmed]
  27. The association between fibrinogen haplotypes and myocardial infarction in men is partly mediated through pleiotropic effects on the serum IL-6 concentration. Mannila, M.N., Eriksson, P., Leander, K., Wiman, B., de Faire, U., Hamsten, A., Silveira, A. J. Intern. Med. (2007) [Pubmed]
  28. No evidence for linkage and association between 4q microsatellite markers and nonsyndromic cleft lip and palate in chilean case-parents trios. Blanco, R., Suazo, J., Santos, J.L., Carreño, H., Palomino, H., Jara, L. The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association. (2005) [Pubmed]
  29. Meiosis study in a population sample from Afghanistan: allele frequencies and mutation rates of 16 STR loci. Hohoff, C., Schürenkamp, M., Börchers, T., Eppink, M., Brinkmann, B. Int. J. Legal Med. (2006) [Pubmed]
  30. Mechanism of human platelet activation by endotoxic glycolipid-bearing mutant Re595 of Salmonella minnesota. Timmons, S., Huzoor-Akbar, n.u.l.l., Grabarek, J., Kloczewiak, M., Hawiger, J. Blood (1986) [Pubmed]
  31. Molecular assessment of post-BMT chimerism using various biologic specimens and automated DNA sizing technology. Jółkowska, J., Wachowiak, J., Lange, A., Kwissa, M., Witt, M. J. Hematother. Stem Cell Res. (2000) [Pubmed]
  32. Association between patterns of nucleotide variation across the three fibrinogen genes and plasma fibrinogen levels: the Coronary Artery Risk Development in Young Adults (CARDIA) study. Reiner, A.P., Carty, C.L., Carlson, C.S., Wan, J.Y., Rieder, M.J., Smith, J.D., Rice, K., Fornage, M., Jaquish, C.E., Williams, O.D., Tracy, R.P., Lewis, C.E., Siscovick, D.S., Boerwinkle, E., Nickerson, D.A. J. Thromb. Haemost. (2006) [Pubmed]
  33. Report of the European DNA profiling group (EDNAP): an investigation of the complex STR loci D21S11 and HUMFIBRA (FGA). Gill, P., d'Aloja, E., Andersen, J., Dupuy, B., Jangblad, M., Johnsson, V., Kloosterman, A.D., Kratzer, A., Lareu, M.V., Meldegaard, M., Phillips, C., Pfitzinger, H., Rand, S., Sabatier, M., Scheithauer, R., Schmitter, H., Schneider, P., Vide, M.C. Forensic Sci. Int. (1997) [Pubmed]
 
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