Browse > Article
http://dx.doi.org/10.5734/JGM.2014.11.1.1

Type 1 diabetes genetic susceptibility markers and their functional implications  

Park, Yongsoo (Department of Internal Medicine, Hanyang University College of Medicine)
Publication Information
Journal of Genetic Medicine / v.11, no.1, 2014 , pp. 1-10 More about this Journal
Abstract
Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by selective destruction of pancreatic ${\beta}$-cells resulting in insulin deficiency. The genetic determinants of T1D susceptibility have been linked to several loci, in particular to the human leukocyte antigen (HLA) region, which accounts for 50% of the genetic risk of developing T1D. Multiple genes in the HLA region, which are in strong linkage disequilibrium, are thought to be involved. Another important locus, with a smaller effect on genetic predisposition to T1D, is the insulin gene. The advent of numerous single nucleotide polymorphism markers and genome screening has enabled the identification of dozens of new T1D susceptibility loci. Some of them appear to predispose to T1D independently of the HLA and may be important in families with T1D who lack strong HLA susceptibility. Other loci may interact with each other to cause susceptibility. The autoimmune response against ${\beta}$-cells can also be triggered by environmental factors in the presence of a predisposing genetic background. Deciphering the environmental and genetic factors involved should help to understand the origin of T1D and aid in the design of individualized prevention programs.
Keywords
Type 1 diabetes mellitus; Autoimmune diseases; Genetics; HLA antigens;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Park Y, Lee H, Koh CS, Min H, Rowley M, Mackay IR, et al. The low prevalence of immunogenetic markers in Korean adult-onset IDDM patients. Diabetes Care 1996;19:241-5.   DOI   ScienceOn
2 Gianani R, Eisenbarth GS. The stages of type 1A diabetes: 2005. Immunol Rev 2005;204:232-49.   DOI
3 Park Y, Eisenbarth GS. Aetiology and epidemiology of type 1 diabetes. Topic Endocrinol 1998;10:2-6.
4 Park Y, Lee H, Takino H, Abiru N, Kawasaki E, Eisenbarth GS. Evaulation of the efficacy of the combination of multiple autoantibodies to isletspecific antigens in Korean type 1 diabetic patients. Acta Diabetol 2001; 38:51-6.   DOI
5 Redondo MJ, Jeffrey J, Fain PR, Eisenbarth GS, Orban T. Concordance for islet autoimmunity among monozygotic twins. N Engl J Med 2008;359: 2849-50.   DOI
6 Concannon P, Rich SS, Nepom GT. Genetics of type 1A diabetes. N Engl J Med 2009;360:1646-54.   DOI   ScienceOn
7 Eisenbarth GS. Type I diabetes mellitus. A chronic autoimmune disease. N Engl J Med 1986;314:1360-8.   DOI   ScienceOn
8 Ikegami H, Fujisawa T, Makino S, Ogihara T. Congenic mapping and candidate sequencing of susceptibility genes for Type 1 diabetes in the NOD mouse. Ann N Y Acad Sci 2003;1005:196-204.   DOI
9 Steck AK, Rewers MJ. Genetics of type 1 diabetes. Clin Chem 2011;57: 176-85.   DOI
10 She JX, Marron MP. Genetic susceptibility factors in type 1 diabetes: linkage disequilibrium and functional analyses. Curr Opin Immunol 1998;10:682-9.   DOI
11 Park Y, Eisenbarth GS. Genetic susceptibility factors of Type 1 diabetes in Asians. Diabetes Metab Res Rev 2001;17:2-11.   DOI
12 Concannon P, Erlich HA, Julier C, Morahan G, Nerup J, Pociot F, et al. Type 1 diabetes: evidence for susceptibility loci from four genome-wide linkage scans in 1,435 multiplex families. Diabetes 2005;54:2995-3001.   DOI
13 Lander E, Kruglyak L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet 1995;11:241-7.   DOI   ScienceOn
14 Park Y. Functional evaluation of the type 1 diabetes (T1D) susceptibility candidate genes. Diabetes Res Clin Pract 2007;77(Suppl 1):S110-5.   DOI
15 Park Y, Wang CY, Ko KW, Yang SW, Park M, Yang MC, et al. Combinations of HLA DR and DQ molecules determine the susceptibility to insulindependent diabetes mellitus in Koreans. Hum Immunol 1998;59:794-801.   DOI   ScienceOn
16 Park Y, She JX, Noble JA, Erlich HA, Eisenbarth GS. Transracial evidence for the influence of the homologous HLA DR-DQ haplotype on transmission of HLA DR4 haplotypes to diabetic children. Tissue Antigens 2001;57:185-91.   DOI
17 Park Y, She JX, Wang CY, Lee H, Babu S, Erlich HA, et al. Common susceptibility and transmission pattern of human leukocyte antigen DRB1-DQB1 haplotypes to Korean and Caucasian patients with type 1 diabetes. J Clin Endocrinol Metab 2000;85:4538-42.
18 Patterson CC, Dahlquist GG, Gyurus E, Green A, Soltesz G; EURODIAB Study Group. Incidence trends for childhood type 1 diabetes in Europe during 1989-2003 and predicted new cases 2005-20: a multicentre prospective registration study. Lancet 2009;373:2027-33.   DOI   ScienceOn
19 Karvonen M, Viik-Kajander M, Moltchanova E, Libman I, LaPorte R, Tuomilehto J. Incidence of childhood type 1 diabetes worldwide. Diabetes Mondiale (DiaMond) Project Group. Diabetes Care 2000;23:1516-26.   DOI   ScienceOn
20 Fernando MM, Stevens CR, Walsh EC, De Jager PL, Goyette P, Plenge RM, et al. Defining the role of the MHC in autoimmunity: a review and pooled analysis. PLoS Genet 2008;4:e1000024.   DOI
21 Lieberman SM, Evans AM, Han B, Takaki T, Vinnitakaya Y, Caldwell JA, et al. Identification of the beta cell antigen targeted by a prevalent population of pathogenic CD8+ T cells in autoimmune diabetes. Proc Natl Acad Sci U S A 2003;100:8384-8.   DOI   ScienceOn
22 Noble JA, Martin A, Valdes AM, Lane JA, Galgani A, Petrone A, et al. Type 1 diabetes risk for human leukocyte antigen (HLA)-DR3 haplotypes depends on genotypic context: association of DPB1 and HLA class I loci among DR3- and DR4-matched Italian patients and controls. Hum Immunol 2008;69:291-300.   DOI
23 Zake LN, Ghaderi M, Park Y, Babu S, Eisenbarth G, Sanjeevi CB. MHC class I chain-related gene alleles 5 and 5.1 are transmitted more frequently to type 1 diabetes offspring in HBDI families. Ann N Y Acad Sci 2002;958:309-11.
24 Howson JM, Walker NM, Clayton D, Todd JA; Type 1 Diabetes Genetics Consortium. Confirmation of HLA class II independent type 1 diabetes associations in the major histocompatibility complex including HLA-B and HLA-A. Diabetes Obes Metab 2009;11(Suppl 1):31-45.   DOI
25 Suemizu H, Radosavljevic M, Kimura M, Sadahiro S, Yoshimura S, Bahram S, et al. A basolateral sorting motif in the MICA cytoplasmic tail. Proc Natl Acad Sci U S A 2002;99:2971-6.   DOI
26 Park Y, Lee H, Sanjeevi CB, Eisenbarth GS. MICA polymorphism is associated with type 1 diabetes in the Korean population. Diabetes Care 2001;24:33-8.   DOI   ScienceOn
27 Lucassen AM, Julier C, Beressi JP, Boitard C, Froguel P, Lathrop M, et al. 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;4:305-10.   DOI   ScienceOn
28 Pugliese A, Zeller M, Fernandez A Jr, Zalcberg LJ, Bartlett RJ, Ricordi C, et al. 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;15:293-7.   DOI
29 Ueda H, Howson JM, Esposito L, Heward J, Snook H, Chamberlain G, et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 2003;423:506-11.   DOI   ScienceOn
30 Ikegami H, Awata T, Kawasaki E, Kobayashi T, Maruyama T, Nakanishi K, et al. The association of CTLA4 polymorphism with type 1 diabetes is concentrated in patients complicated with autoimmune thyroid disease: a multicenter collaborative study in Japan. J Clin Endocrinol Metab 2006; 91:1087-92.   DOI
31 Hill RJ, Zozulya S, Lu YL, Ward K, Gishizky M, Jallal B. The lymphoid protein tyrosine phosphatase Lyp interacts with the adaptor molecule Grb2 and functions as a negative regulator of T-cell activation. Exp Hematol 2002 Mar;30(3):237-44.
32 Morahan G, Huang D, Ymer SI, Cancilla MR, Stephen K, Dabadghao P, et al. Linkage disequilibrium of a type 1 diabetes susceptibility locus with a regulatory IL12B allele. Nat Genet 2001;27:218-21.   DOI
33 Onengut-Gumuscu S, Ewens KG, Spielman RS, 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: 678-80.   DOI
34 Bottini N, Musumeci L, Alonso A, Rahmouni S, Nika K, Rostamkhani M, et al. A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat Genet 2004;36:337-8.   DOI   ScienceOn
35 Nerup J, Pociot F; European Consortium for IDDM Studies. A genomewide scan for type 1-diabetes susceptibility in Scandinavian families: identification of new loci with evidence of interactions. Am J Hum Genet 2001; 69:1301-13.   DOI
36 Vella A, Cooper JD, Lowe CE, Walker N, Nutland S, Widmer B, et al. Localization of a type 1 diabetes locus in the IL2RA/CD25 region by use of tag single-nucleotide polymorphisms. Am J Hum Genet 2005;76:773-9.   DOI   ScienceOn
37 Todd JA, Walker NM, Cooper JD, Smyth DJ, Downes K, Plagnol V, et al. Robust associations of four new chromosome regions from genomewide analyses of type 1 diabetes. Nat Genet 2007;39:857-64.   DOI
38 Hakonarson H, Grant SF, Bradfield JP, Marchand L, Kim CE, Glessner JT, et al. A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene. Nature 2007;448:591-4.   DOI   ScienceOn
39 Concannon P, Onengut-Gumuscu S, Todd JA, Smyth DJ, Pociot F, Bergholdt R, et al; Type 1 Diabetes Genetics Consortium. A human type 1 diabetes susceptibility locus maps to chromosome 21q22.3. Diabetes 2008;57: 2858-61.   DOI
40 Mirel DB, Valdes AM, Lazzeroni LC, Reynolds RL, Erlich HA, Noble JA. Association of IL4R haplotypes with type 1 diabetes. Diabetes 2002;51: 3336-41.   DOI   ScienceOn
41 Biason-Lauber A, Boehm B, Lang-Muritano M, Gauthier BR, Brun T, Wollheim CB, et al. Association of childhood type 1 diabetes mellitus with a variant of PAX4: possible link to beta cell regenerative capacity. Diabetologia 2005;48:900-5.   DOI
42 Ikegami H, Ogihara T. Genetics of insulin-dependent diabetes mellitus. Endocr J 1996;43:605-13.   DOI   ScienceOn
43 Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD, Erlich HA, et al; Type 1 Diabetes Genetics Consortium. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet 2009;41:703-7.   DOI   ScienceOn
44 Cooper JD, Walker NM, Smyth DJ, Downes K, Healy BC, Todd JA; Type I Diabetes Genetics Consortium. Follow-up of 1715 SNPs from the Wellcome Trust Case Control Consortium genome-wide association study in type I diabetes families. Genes Immun 2009;10(Suppl 1):S85-94.   DOI
45 Bradfield JP, Qu HQ, Wang K, Zhang H, Sleiman PM, Kim CE, et al. A genome-wide meta-analysis of six type 1 diabetes cohorts identifies multiple associated loci. PLoS Genet 2011;7:e1002293.   DOI
46 Park Y. Why is type 1 diabetes uncommon in Asia? Ann NY Acad Sci 2006;1079:31-40.   DOI
47 Imagawa A, Hanafusa T, Miyagawa J, Matsuzawa Y. A novel subtype of type 1 diabetes mellitus characterized by a rapid onset and an absence of diabetes-related antibodies. Osaka IDDM Study Group. N Engl J Med 2000;342:301-7.   DOI   ScienceOn
48 Cho YM, Kim JT, Ko KS, Koo BK, Yang SW, Park MH, et al. Fulminant type 1 diabetes in Korea: high prevalence among patients with adult-onset type 1 diabetes. Diabetologia 2007;50:2276-9.   DOI   ScienceOn
49 Park Y, Hong S, Park L, Woo J, Baik S, Nam M, et al; KNDP Collaboratory Group. LADA prevalence estimation and insulin dependency during follow-up. Diabetes Metab Res Rev 2011;27:975-9.   DOI
50 Diez J, Park Y, Zeller M, Brown D, Garza D, Ricordi C, et al. Differential splicing of the IA-2 mRNA in pancreas and lymphoid organs as a permissive genetic mechanism for autoimmunity against the IA-2 type 1 diabetes autoantigen. Diabetes 2001;50:895-900.   DOI