Association of -23 HphI, a polymorphic marker of the INS gene, with type 1 diabetes mellitus
https://doi.org/10.14341/2072-0351-5668
Abstract
Aim.
To analyse frequency distribution of alleles and genotypes of -23 HphI, a polymorphic marker of the INS gene, for evaluation of its associationwith DM1.
Materials and methods.
The study included two group of subjects: healthy ones and DM1 patients. Genotyping was performed by real time amplification.
Results.
Comparative analysis demonstrated association between -23 HphI polymorphic marker of INS gene, and type 1 diabetes mellitus.
Conclusion.
The use of the case-control method revealed association of -23 HphI, a polymorphic marker of the INS gene, with type 1 diabetes mellitus.
To analyse frequency distribution of alleles and genotypes of -23 HphI, a polymorphic marker of the INS gene, for evaluation of its associationwith DM1.
Materials and methods.
The study included two group of subjects: healthy ones and DM1 patients. Genotyping was performed by real time amplification.
Results.
Comparative analysis demonstrated association between -23 HphI polymorphic marker of INS gene, and type 1 diabetes mellitus.
Conclusion.
The use of the case-control method revealed association of -23 HphI, a polymorphic marker of the INS gene, with type 1 diabetes mellitus.
About the Authors
Aleksey Georgievich Nikitin
Endocrinology Research Centre, Moscow
Elena Yur'evna Lavrikova
State Research Institute of Genetics and Selection of Industrial Microorganisms, Moscow
Yury Alexandrovich Seregin
State Research Institute of Genetics and Selection of Industrial Microorganisms, Moscow
Lyubov' Iosifovna Zil'berman
Endocrinology Research Centre, Moscow
Nana Mikhailovna Tsitlidze
Endocrinology Research Centre, Moscow
Tamara Leonidovna Kuraeva
Endocrinology Research Centre, Moscow
Valentina Alexandrovna Peterkova
Endocrinology Research Centre, Moscow
Ivan Ivanovich Dedov
Endocrinology Research Centre, Moscow
Valery Vyacheslavovich Nosikov
State Research Institute of Genetics and Selection of Industrial Microorganisms, Moscow
References
1. Devendra D., Liu E., Eisenbarth G.S. Type 1 diabetes: recent developments // BMJ. - 2004. - 328 (7442). - P. 750-754.
2. Knip M., Veijola R., Virtanen S.M., Hyцty H., Vaarala O., Akerblom H.K. Environmental triggers and determinants of type 1 diabetes // Diabetes. - 2005. - 54 Suppl. 2. - P. S125-136.
3. Foulis A.K. The pathology of the endocrine pancreas in type 1 (insulin-dependent) diabetes mellitus // APMIS. - 1996. - 104 (3). - P. 161-167.
4. Miao D., Yu L., Eisenbarth G.S. Role of autoantibodies in type 1 diabetes // Front. Biosci. - 2007. - 12. - P. 1889-1898.
5. Nerup J., Platz P., Andersen O.O., Christy M., Lyngsoe J., Poulsen J.E., Ryder L.P., Thomsen M., Nielsen L.S., Svejgaard A. HL-A ANTIGENS AND DIABETES MELLITUS // The Lancet. - 1974. - 304 (7885). - P. 864-866.
6. Noble J.A., Valdes A.M., Cook M., Klitz W., Thomson G., Erlich H.A. The role of HLA class II genes in insulin-dependent diabetes mellitus: molecular analysis of 180 Caucasian, multiplex families // Am. J. Hum. Genet. - 1996. - 59 (5). - P. 1134-1148.
7. Cucca F., Lampis R., Congia M., Angius E., Nutland S., Bain S.C., Barnett A.H., Todd J.A. A correlation between the relative predisposition of MHC class II alleles to type 1 diabetes and the structure of their proteins // Hum. Mol. Genet. - 2001. - 10 (19). - P. 2025-2037.
8. Kelly M.A., Rayner M.L., Mijovic C.H., Barnett A.H. Molecular aspects of type 1 diabetes // Mol Pathol. - 2003. - 56 (1). - P. 1-10.
9. Devendra D., Eisenbarth G.S. 17. Immunologic endocrine disorders // J. Allergy Clin. Immunol. - 2003. - 111 (2 Suppl). - P. S624-636.
10. Bell G.I., Horita S., Karam J.H. A polymorphic locus near the human insulin gene is associated with insulin-dependent diabetes mellitus // Diabetes. - 1984. - 33 (2). - P. 176-183.
11. Owerbach D., Gabbay K.H. Linkage of the VNTR/insulin-gene and type I diabetes mellitus: increased gene sharing in affected sibling pairs // Am. J. Hum. Genet. - 1994. - 54 (5). - P. 909-912.
12. Lucassen A.M., Julier C., Beressi J., Boitard C., Froguel P., Lathrop M., Bell J.I. Susceptibility to insulin dependent diabetes mellitus maps to a 4.1 kb segment of DNA spanning the insulin gene and associated VNTR // Nat. Genet. - 1993. - 4 (3). - P. 305-310.
13. Bennett S.T., Lucassen A.M., Gough S.C., Powell E.E., Undlien D.E., Pritchard L.E., Merriman M.E., Kawaguchi Y., Dronsfield M.J., Pociot F. Susceptibility to human type 1 diabetes at IDDM2 is determined by tandem repeat variation at the insulin gene minisatellite locus // Nat. Genet. - 1995. - 9 (3). - P. 284-292.
14. Undlien D.E., Bennett S.T., Todd J.A., Akselsen H.E., Ikдheimo I., Reijonen H., Knip M., Thorsby E., Rшnningen K.S. Insulin gene region-encoded susceptibility to IDDM maps upstream of the insulin gene // Diabetes. - 1995. - 44 (6). - P. 620-625.
15. Kristiansen O.P., Larsen Z.M., Pociot F. CTLA-4 in autoimmune diseases-a general susceptibility gene to autoimmunity? // Genes Immun. - 2000. - 1 (3). - P. 170-184.
16. Ueda H., Howson J.M.M., Esposito L., Heward J., Snook, Chamberlain G., Rainbow D.B., Hunter K.M.D., Smith A.N., Di Genova G., Herr M.H., Dahlman I., Payne F., Smyth D., Lowe C., Twells R.C.J., Howlett S., Healy B., Nutland S., Rance H.E., Everett V., Smink L.J., Lam A.C., Cordell H.J., Walker N.M., Bordin C., Hulme J., Motzo C., Cucca F., Hess J.F., Metzker M.L., Rogers J., Gregory S., Allahabadia A., Nithiyananthan R., Tuomilehto-Wolf E., Tuomilehto J., Bingley P., Gillespie K.M., Undlien D.E., Ronningen K.S., Guja C., Ionescu-Tirgoviste C., Savage D.A., Maxwell A.P., Carson D.J., Patterson C.C., Franklyn J.A., Clayton D.G., Peterson L.B., Wicker L.S., Todd J.A., Gough S.C.L. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease // Nature. - 2003. - 423 (6939). - P. 506-511.
17. Nistico L., Buzzetti R., Pritchard L., Van der Auwera B., Giovannini C., Bosi E., Larrad M., Rios M., Chow C., Cockram C., Jacobs K., Mijovic C., Bain S., Barnett A., Vandewalle C., Schuit F., Gorus F., Tosi R., Pozzilli P., Todd J. The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry // Hum. Mol. Genet. - 1996. - 5 (7). - P. 1075-1080.
18. Smyth D., Cooper J.D., Collins J.E., Heward J.M., Franklyn J.A., Howson J.M.M., Vella A., Nutland S., Rance H.E., Maier L., Barratt B.J., Guja C., Ionescu-Tоrgoviste C., Savage D.A., Dunger D.B., Widmer B., Strachan D.P., Ring S.M., Walker N., Clayton D.G., Twells R.C.J., Gough S.C.L., Todd J.A. Replication of an association between the lymphoid tyrosine phosphatase locus (LYP/PTPN22) with type 1 diabetes, and evidence for its role as a general autoimmunity locus // Diabetes. - 2004. - 53 (11). - P. 3020- 3023.
19. Onengut-Gumuscu S., Ewens K.G., Spielman R.S., Concannon P. A functional polymorphism (1858C//T) in the PTPN22 gene is linked and associated with type I diabetes in multiplex families // Genes Immun. - 2004. - 5 (8). - P. 678-680.
20. Bottini N., Musumeci L., Alonso A., Rahmouni S., Nika K., RostamkhaniM., MacMurray J., Meloni G.F., Lucarelli P., Pellecchia M., Eisenbarth G.S., Comings D., Mustelin T. A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes // Nat. Genet. - 2004. - 36 (4). - P. 337- 338.
21. Qu H., Tessier M., Hudson T.J., Polychronakos C. Confirmation of the association of the R620W polymorphism in the protein tyrosine phosphatase PTPN22 with type 1 diabetes in a family based study // J. Med. Genet. - 2005. - 42 (3). - P. 266-270.
22. Kennedy G.C., German M.S., Rutter W.J. The minisatellite in the diabetes susceptibility locus IDDM2 regulates insulin transcription // Nat. Genet. - 1995. - 9 (3). - P. 293-298.
23. Vafiadis P., Bennett S.T., Todd J.A., Nadeau J., Grabs R., Goodyer C.G., Wickramasinghe S., Colle E., Polychronakos C. Insulin expression in human thymus is modulated by INS VNTR alleles at the IDDM2 locus //Nat. Genet. - 1997. - 15 (3). - P. 289-292.
24. Pugliese A., Zeller M., Fernandez A., Zalcberg L.J., Bartlett R.J., Ricordi C., Pietropaolo M., Eisenbarth G.S., Bennett S.T., Patel D.D. The insulin gene is transcribed in the human thymus and transcription levels correlated with allelic variation at the INS VNTR-IDDM2 susceptibility locus for type 1 diabetes //Nat. Genet. - 1997. - 15 (3). - P. 293-297.
25. Le Stunff C., Fallin D., Schork N.J., Bougnиres P. The insulin gene VNTR is associated with fasting insulin levels and development of juvenile obesity // Nat. Genet. - 2000. - 26 (4). - P. 444-446.
26. Bell G.I., Selby M.J., Rutter W.J. The highly polymorphic region near the human insulin gene is composed of simple tandemly repeating sequences // Nature. - 1982. - 295 (5844). - P. 31-35.
27. Krбlovicovб J., Gaunt T.R., Rodriguez S., Wood P.J., Day I.N.M., Vorechovsky I. Variants in the human insulin gene that affect pre-mRNA splicing: is -23HphI a functional single nucleotide polymorphism at IDDM2? // Diabetes. - 2006. - 55 (1). - P. 260-264.
28. Laub O., Rutter W. Expression of the human insulin gene and cDNA in a heterologous mammalian system // J. Biol. Chem. - 1983. - 258 (10). - P. 6043-6050.
29. Marchand L., Polychronakos C. Evaluation of polymorphic splicing in the mechanism of the association of the insulin gene with diabetes // Diabetes. - 2007. - 56 (3). - P. 709-713.
30. Johns M.B., Paulus-Thomas J.E. Purification of human genomic DNA from whole blood using sodium perchlorate in place of phenol // Anal. Biochem. - 1989. - 180 (2). - P. 276-278.
31. Калькулятор для расчета статистики в исследованиях "случай-конт- роль" [http://test.tapotili.ru/calculator_or.php].
32. Kozak M. Leader length and secondary structure modulate mRNA function under conditions of stress // Mol. Cell. Biol. - 1988. - 8 (7). - P. 2737- 2744.
33. Sospedra M., Ferrer-Francesch X., Dominguez O., Juan M., Foz-SalaM., Pujol-Borrell R. Transcription of a broad range of self-antigens in human thymus suggests a role for central mechanisms in tolerance toward peripheral antigens // J. Immunol. - 1998. - 161 (11). - P. 5918-5929.
34. Kent S.C., Chen Y., Bregoli L., Clemmings S.M., Kenyon N.S., Ricordi C., Hering B.J., Hafler D.A. Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope // Nature. - 2005. - 435 (7039). - P. 224-228.
35. Hassainya Y., Garcia-Pons F., Kratzer R., Lindo V., Greer F., Lemonnier F.A., Niedermann G., van Endert P.M. Identification of naturally processed HLAA2- restricted proinsulin epitopes by reverse immunology // Diabetes. - 2005. - 54 (7). - P. 2053-2059.
36. Kent S., Hafler D. OR.72. Enhanced Recognition of Insulin a Chain 1-15 By Expanded T-Cell Clones from Human Type 1 Diabetic (T1D) Pancreatic Draining Lymph Nodes // Clinical Immunology. - 2006. - 119 (Supplement 1). - P. S30-S31.
37. Pugliese A., Brown D., Garza D., Murchison D., Zeller M., Redondo M.J., Redondo M., Diez J., Eisenbarth G.S., Patel D.D., Ricordi C. Self-antigenpresenting cells expressing diabetes-associated autoantigens exist in both thymus and peripheral lymphoid organs // J. Clin. Invest. - 2001. - 107 (5). - P. 555-564.
38. Hansen S.K., Gjesing A.P., Rasmussen S.K., Glьmer C., Urhammer S.A., Andersen G., Rose C.S., Drivsholm T., Torekov S.K., Jensen D.P., Ekstrшm C.T., Borch-Johnsen K., Jшrgensen T., McCarthy M.I., Hansen T., Pedersen O. Large-scale studies of the HphI insulin gene variable-numberof- tandem-repeats polymorphism in relation to Type 2 diabetes mellitus and insulin release // Diabetologia. - 2004. - 47 (6). - P. 1079-1087.
39. Nakayama M., Abiru N., Moriyama H., Babaya N., Liu E., Miao D., Yu L., Wegmann D.R., Hutton J.C., Elliott J.F., Eisenbarth G.S. Prime role for an insulin epitope in the development of type[thinsp]1 diabetes in NOD mice // Nature. - 2005. - 435 (7039). - P. 220-223.
40. Schatz D.A., Bingley P.J. Update on major trials for the prevention of type 1 diabetes mellitus: the American Diabetes Prevention Trial (DPT-1) and the European Nicotinamide Diabetes Intervention Trial (ENDIT) // J. Pediatr. Endocrinol. Metab. - 2001. - 14 Suppl 1. - P. 619-622.
41. Skyler J.S., Krischer J.P., Wolfsdorf J., Cowie C., Palmer J.P., Greenbaum C., Cuthbertson D., Rafkin-Mervis L.E., Chase H.P., Leschek E. Effects of oral insulin in relatives of patients with type 1 diabetes: The Diabetes Prevention Trial-Type 1 // Diabetes Care. - 2005. - 28 (5). - P. 1068-1076.
42. Hermann R., Laine A., Veijola R., Vahlberg T., Simell S., Lдhde J., Simell O., Knip M., Ilonen J. The effect of HLA class II, insulin and CTLA4 gene regions on the development of humoral beta cell autoimmunity // Diabetologia. - 2005. - 48 (9). - P. 1766-1775.
43. Skyler J.S., Greenbaum C.J., Lachin J.M., Leschek E., Rafkin-Mervis L., Savage P., Spain L. Type 1 Diabetes TrialNet-an international collaborative clinical trials network // Ann. N. Y. Acad. Sci. - 2008. - 1150. - P. 14- 24.
44. Kyewski B., Derbinski J. Self-representation in the thymus: an extended view // Nat. Rev. Immunol. - 2004. - 4 (9). - P. 688-698.
45. Palumbo M.O., Levi D., Chentoufi A.A., Polychronakos C. Isolation and characterization of proinsulin-producing medullary thymic epithelial cell clones // Diabetes. - 2006. - 55 (9). - P. 2595-2601.
Review
For citations:
Nikitin A.G., Lavrikova E.Yu., Seregin Yu.A., Zil'berman L.I., Tsitlidze N.M., Kuraeva T.L., Peterkova V.A., Dedov I.I., Nosikov V.V. Association of -23 HphI, a polymorphic marker of the INS gene, with type 1 diabetes mellitus. Diabetes mellitus. 2010;13(2):17-20. (In Russ.) https://doi.org/10.14341/2072-0351-5668
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