Posible implicación del gen RNASEH1 en la etiología de diabetes mellitus tipo 1

Resumen

Las enfermedades complejas se caracterizan porque presentan varios genes además de factores ambientales implicados en su etiología. Las bases genéticas de la diabetes mellitus tipo 1 (T1D) supone un efecto mayor del complejo HLA que interactúa con otros genes y con el ambiente. Mucho se ha descrito acerca de la posible participación de las infecciones virales como desencadenadores de T1D. En esta revisión exploramos los posibles mecanismos por los cuales el gen RNASEH1 podría estar participando en la etiología de T1D, a partir de una infección viral. El gen RNASEH1 se localiza en la región cromosómica 2p25, la cual ha sido recientemente implicada por nosotros en la susceptibilidad a T1D. Este gen ha sido implicado en la enfermedad mediante análisis genético. Acá pretendemos dar sentido biológico a los datos genéticos. Considerando que la enfermedad es multifactorial, este planteamiento no excluye la participación de otros genes u otros factores ambientales.

Palabras clave:

diabetes tipo 1

susceptibilidad genética

gen RNASEH1

factores ambientales

type 1 diabetes

genetic susceptibility

RNASEH1 gene

environmental factors

Citas

Kyvik KO, Green A, Beck-Nielsen H. Concordance rates of insulin dependent diabetes mellitus: a population based study of young Danish twins. BMJ (Clinical research ed.) 1995;311(7010):913-7.

Kim MS, Polychronakos C. Immunogenetics of type 1 diabetes. Hormone research 2005;64(4):180-8.

Nerup J, Platz P, Andersen OO, Christy M, Lyngsoe J, Poulsen JE, et al. HL-A antigens and diabetes mellitus. Lancet 1974;2(7885):864-6.

Cudworth AG, Woodrow JC. Evidence for HL-A-linked genes in “juvenile” diabetes mellitus. British medical journal 1975;3(5976):133-5.

Uribe F, Pineda-Trujillo N, Montoya F, Latorre G, Villegas A, Cerón J, et al. Análisis de ligamiento genético de la diabetes mellitus tipo 1 a marcadores de los cromosomas 2 y 11 en familias antioqueñas. IATREIA 2004;17(2):93-104.

Pineda-Trujillo N, Uribe F, Montoya F, J-M A, Latorre G, Villegas A, et al. 2p25 is linked and associated to Type 1 Diabetes in Colombia. Clin Genetics submitted; 2009.

Cerritelli SM, Crouch RJ. Cloning, expression, and mapping of ribonucleases H of human and mouse related to bacterial RNase HI. Genomics 1998;53(3):300-7.

Istrail S, Sutton GG, Florea L, Halpern AL, Mobarry CM, Lippert R, et al. Whole-genome shotgun assembly and comparison of human genome assemblies. Proceedings of the National Academy of Sciences of the United States of America 2004;101(7):1916-21.

ten Asbroek AL, van Groenigen M, Jakobs ME, Koevoets C, Janssen B, Baas F. Ribonuclease H1 maps to chromosome 2 and has at least three pseudogene loci in the human genome. Genomics 2002;79(6):818-23.

Lyamichev V, Brow MA, Dahlberg JE. Structure-specific endonucleolytic cleavage of nucleic acids by eubacterial DNA polymerases. Science (New York, NY) 1993;260(5109):778-83.

Nowotny M, Gaidamakov SA, Ghirlando R, Cerritelli SM, Crouch RJ, Yang W. Structure of human RNase H1 complexed with an RNA/DNA hybrid: insight into HIV reverse transcription. Molecular cell 2007;28(2):264-76.

Itaya M, Omori A, Kanaya S, Crouch RJ, Tanaka T, Kondo K. Isolation of RNase H genes that are essential for growth of Bacillus subtilis 168. Journal of bacteriology 1999;181(7):2118-23.

Cerritelli SM, Frolova EG, Feng C, Grinberg A, Love PE, Crouch RJ. Failure to produce mitochondrial DNA results in embryonic lethality in RNaseh1 null mice. Molecular cell 2003;11(3):807-15.

Broccoli S, Rallu F, Sanscartier P, Cerritelli SM, Crouch RJ, Drolet M. Effects of RNA polymerase modifications on transcription-induced negative supercoiling and associated R-loop formation. Molecular microbiology 2004;52(6):1769-79.

Katayanagi K, Miyagawa M, Matsushima M, Ishikawa M, Kanaya S, Ikehara M, et al. Three-dimensional structure of ribonuclease H from E. coli. Nature 1990;347(6290):306-9.

Tsunaka Y, Haruki M, Morikawa M, Kanaya S. Strong nucleic acid binding to the Escherichia coli RNase HI mutant with two arginine residues at the active site. Biochimica et biophysica acta 2001;1547(1):135-42.

Keller W, Crouch R. Degradation of DNA RNA hybrids by ribonuclease H and DNA polymerases of cellular and viral origin. Proceedings of the National Academy of Sciences of the United States of America 1972;69(11):3360-4.

Repaske R, Hartley JW, Kavlick MF, O’Neill RR, Austin JB. Inhibition of RNase H activity and viral replication by single mutations in the 3’ region of Moloney murine leukemia virus reverse transcriptase. Journal of virology 1989;63(3):1460-4.

Klumpp K, Mirzadegan T. Recent progress in the design of small molecule inhibitors of HIV RNase H. Current pharmaceutical design 2006;12(15):1909-22.

Blain SW, Goff SP. Nuclease activities of Moloney murine leukemia virus reverse transcriptase. Mutants with altered substrate specificities. The Journal of biological chemistry 1993;268(31):23585-92.

Ben-Artzi H, Zeelon E, Gorecki M, Panet A. Double-stranded RNA-dependent RNase activity associated with human immunodeficiency virus type 1 reverse transcriptase. Proceedings of the National Academy of Sciences of the United States of America 1992;89(3):927-31.

Cerritelli SM, Crouch RJ. The non-RNase H domain of Saccharomyces cerevisiae RNase H1 binds double-stranded RNA: magnesium modulates the switch between double-stranded RNA binding and RNase H activity. RNA (New York, NY) 1995;1(3):246-59.

Pearl-Yafe M, Kaminitz A, Yolcu ES, Yaniv I, Stein J, Askenasy N. Pancreatic islets under attack: cellular and molecular effectors. Current pharmaceutical design 2007;13(7):749-60.

Kantarova D, Buc M. Genetic susceptibility to type 1 diabetes mellitus in humans. Physiological research / Academia Scientiarum Bohemoslovaca 2007;56(3):255-66.

Peng H, Hagopian W. Environmental factors in the development of Type 1 diabetes. Reviews in endocrine & metabolic disorders 2006;7(3):149-62.

Sf A. the seasonal variation in the onset of acute diabetes. Arch intern med 1926;27:861-2.

Kurtz F, Juif JG, Hauptmann GR. Virologic, immunologic, and genetic factors in insulin-dependent diabetes mellitus. The Journal of pediatrics 1983;102(5):800.

Green J, Casabonne D, Newton R. Coxsackie B virus serology and Type 1 diabetes mellitus: a systematic review of published case-control studies. Diabet Med 2004;21(6):507-14.

Drescher KM, Tracy SM. The CVB and etiology of type 1 diabetes. Current topics in microbiology and immunology 2008;323:259-74.

Menser MA, Forrest JM, Bransby RD. Rubella infection and diabetes mellitus. Lancet 1978;1(8055):57-60.

Numazaki K, Goldman H, Wong I, Wainberg MA. Infection of cultured human fetal pancreatic islet cells by rubella virus. American journal of clinical pathology 1989;91(4):446-51.

Ilonen J, Salonen R, Salmi A, Mustonen A. Low levels of mumps virus antigen induced interferon-alpha production in insulin-dependent diabetes. Diabetes research (Edinburgh, Scotland) 1989;12(2):75-8.

Aarnisalo J, Veijola R, Vainionpaa R, Simell O, Knip M, Ilonen J. Cytomegalovirus infection in early infancy: risk of induction and progression of autoimmunity associated with type 1 diabetes. Diabetologia 2008;51(5):769-72.

van der Werf N, Hillebrands JL, Klatter FA, Bos I, Bruggeman CA, Rozing J. Cytomegalovirus infection modulates cellular immunity in an experimental model for autoimmune diabetes. Clinical & developmental immunology 2003;10(2-4):153-60.

Chikazawa K, Okusa H, Minakami H, Kimura K, Araki S, Tamada T. [Acute onset of insulin-dependent diabetes mellitus caused by Epstein-Barr virus infection]. Nippon Sanka Fujinka Gakkai zasshi 1985;37(3):453-6.

Jali MV, Shankar PS. Transient diabetes following chicken pox. The Journal of the Association of Physicians of India 1990;38(9):663-4.

Choi KS, Jun HS, Kim HN, Park HJ, Eom YW, Noh HL, et al. Role of Hck in the pathogenesis of encephalomyocarditis virus-induced diabetes in mice. Journal of virology 2001;75(4):1949-57.

Yama S, Nishioka W, Hirokami Y, Setoguchi R, Takeyama N, Saeki K, et al. Effects of tacrolimus (FK506) on encephalomyocarditic virus-induced diabetes in mice. Microbiology and immunology 2004;48(1):7-13.

Jun HS, Yoon JW. A new look at viruses in type 1 diabetes. Diabetes/metabolism research and reviews 2003;19(1):8-31.

Campbell IL, Harrison LC, Ashcroft RG, Jack I. Reovirus infection enhances expression of class I MHC proteins on human beta-cell and rat RINm5F cell. Diabetes 1988;37(3):362-5.

Onodera T, Jenson AB, Yoon JW, Notkins AL. Virus-induced diabetes mellitus: reovirus infection of pancreatic beta cells in mice. Science (New York, NY) 1978;201(4355):529-31.

Yoon JW, Onodera T, Notkins AL. Virus-induced diabetes mellitus. XV. Beta cell damage and insulindependent hyperglycemia in mice infected with coxsackie virus B4. The Journal of experimental medicine 1978;148(4):1068-80.

Hou J, Sheikh S, Martin DL, Chatterjee NK. Coxsackievirus B4 alters pancreatic glutamate decarboxylase expression in mice soon after infection. Journal of autoimmunity 1993;6(5):529-42.

Yoon JW, London WT, Curfman BL, Brown RL, Notkins AL. Coxsackie virus B4 produces transient diabetes in nonhuman primates. Diabetes 1986;35(6):712-6.

Rayfield EJ, Kelly KJ, Yoon JW. Rubella virus-induced diabetes in the hamster. Diabetes 1986;35(11):1278-81.

Tajima M, Yazawa T, Hagiwara K, Kurosawa T, Takahashi K. Diabetes mellitus in cattle infected with bovine viral diarrhea mucosal disease virus. Zentralblatt fur Veterinarmedizin 1992;39(8):616-20.

Blankenhorn EP, Rodemich L, Martin-Fernández C, Leif J, Greiner DL, Mordes JP. The rat diabetes susceptibility locus Iddm4 and at least one additional gene are required for autoimmune diabetes induced by viral infection. Diabetes 2005;54(4):1233-7.

Zipris D, Lien E, Xie JX, Greiner DL, Mordes JP, Rossini AA. TLR activation synergizes with Kilham rat virus infection to induce diabetes in BBDR rats. J Immunol 2005;174(1):131-42.

Jenson AB, Rosenberg HS, Notkins AL. Pancreatic islet-cell damage in children with fatal viral infections. Lancet 1980;2(8190):354-8.

Ylipaasto P, Klingel K, Lindberg AM, Otonkoski T, Kandolf R, Hovi T, et al. Enterovirus infection in human pancreatic islet cells, islet tropism in vivo and receptor involvement in cultured islet beta cells. Diabetologia 2004;47(2):225-39.

Chehadeh W, Weill J, Vantyghem MC, Alm G, Lefebvre J, Wattre P, et al. Increased level of interferonalpha in blood of patients with insulin-dependent diabetes mellitus: relationship with coxsackievirus B infection. The Journal of infectious diseases 2000;181(6):1929-39.

Bogdan C. The function of type I interferons in antimicrobial immunity. Current opinion in immunology 2000;12(4):419-24.

Barber GN. Host defense, viruses and apoptosis. Cell death and differentiation 2001;8(2):113-26.

Player MR, Kalinichenko EN, Podkopaeva TL, Mikhailopulo IA, Seela F, Torrence PF. Dissection of the roles of adenine ring nitrogen (N-1) and exocyclic amino (N-6) moieties in the interaction of 2-5A with RNase L. Biochemical and biophysical research communications 1998;245(2):430-4.

Silverman RH. A scientific journey through the 2-5A/RNase L system. Cytokine & growth factor reviews 2007;18(5-6):381-8.

Flodstrom-Tullberg M, Hultcrantz M, Stotland A, Maday A, Tsai D, Fine C, et al. RNase L and doublestranded RNA-dependent protein kinase exert complementary roles in islet cell defense during coxsackievirus infection. J Immunol 2005;174(3):1171-7.

Jun HS, Yoon JW. The role of viruses in type I diabetes: two distinct cellular and molecular pathogenic mechanisms of virus-induced diabetes in animals. Diabetologia 2001;44(3):271-85.

Filippi C, von Herrath M. How viral infections affect the autoimmune process leading to type 1 diabetes. Cellular immunology 2005;233(2):125-32.

Player MR, Torrence PF. The 2-5A system: modulation of viral and cellular processes through acceleration of RNA degradation. Pharmacology & therapeutics 1998;78(2):55-113.