Current Diabetes Reports

, 11:533 | Cite as

Genetics of the HLA Region in the Prediction of Type 1 Diabetes

  • Janelle A. NobleEmail author
  • Ana M. Valdes
Genetics (Jose C. Florez, Section Editor)


Type 1 diabetes (T1D) is one of the most widely studied complex genetic disorders, and the genes in HLA are reported to account for approximately 40–50% of the familial aggregation of T1D. The major genetic determinants of this disease are polymorphisms of class II HLA genes encoding DQ and DR. The DR-DQ haplotypes conferring the highest risk are DRB1*03:01-DQA1*05:01-DQB1*02:01 (abbreviated “DR3”) and DRB1*04:01/02/04/05/08-DQA1*03:01-DQB1*03:02/04 (or DQB1*02; abbreviated “DR4”). The risk is much higher for the heterozygote formed by these two haplotypes (OR = 16.59; 95% CI, 13.7–20.1) than for either of the homozygotes (DR3/DR3, OR = 6.32; 95% CI, 5.12–7.80; DR4/DR4, OR = 5.68; 95% CI, 3.91). In addition, some haplotypes confer strong protection from disease, such as DRB1*15:01-DQA1*01:02-DQB1*06:02 (abbreviated “DR2”; OR = 0.03; 95% CI, 0.01–0.07). After adjusting for the genetic correlation with DR and DQ, significant associations can be seen for HLA class II DPB1 alleles, in particular, DPB1*04:02, DPB1*03:01, and DPB1*02:02. Outside of the class II region, the strongest susceptibility is conferred by class I allele B*39:06 (OR =10.31; 95% CI, 4.21–25.1) and other HLA-B alleles. In addition, several loci in the class III region are reported to be associated with T1D, as are some loci telomeric to class I. Not surprisingly, current approaches for the prediction of T1D in screening studies take advantage of genotyping HLA-DR and HLA-DQ loci, which is then combined with family history and screening for autoantibodies directed against islet-cell antigens. Inclusion of additional moderate HLA risk haplotypes may help identify the majority of children with T1D before the onset of the disease.


Type 1 diabetes Genetic risk HLA class II HLA class I HLA class III Risk prediction 



This work was supported by National Institutes of Health R01 DK61722 (J.A.N.).


No potential conflicts of interest relevant to this article were reported.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    • Eisenbarth GS: Banting Lecture 2009: An unfinished journey: molecular pathogenesis to prevention of type 1A diabetes. Diabetes 2010, 59:759–774. This lecture gives an excellent overview of T1D pathogenesis important to the understanding of the genetic susceptibility. PubMedCrossRefGoogle Scholar
  2. 2.
    Dunger DB, Sperling MA, Acerini CL, Bohn DJ, Daneman D, Danne TP, et al. European Society for Paediatric Endocrinology/Lawson Wilkins Pediatric Endocrine Society consensus statement on diabetic ketoacidosis in children and adolescents. Pediatrics. 2004;113:e133–40.PubMedCrossRefGoogle Scholar
  3. 3.
    Maahs DM, West NA, Lawrence JM, Mayer-Davis EJ. Epidemiology of type 1 diabetes. Endocrinol Metab Clin North Am. 2010;39:481–97.PubMedCrossRefGoogle Scholar
  4. 4.
    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.PubMedCrossRefGoogle Scholar
  5. 5.
    Dabelea D, Bell RA, D'Agostino Jr RB, Imperatore G, Johansen JM, Linder B, et al. Incidence of diabetes in youth in the United States. Jama. 2007;297:2716–24.PubMedCrossRefGoogle Scholar
  6. 6.
    Concannon P, Rich SS, Nepom GT. Genetics of type 1A diabetes. N Engl J Med. 2009;360:1646–54.PubMedCrossRefGoogle Scholar
  7. 7.
    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.PubMedCrossRefGoogle Scholar
  8. 8.
    Bonifacio E, Ziegler AG. Advances in the prediction and natural history of type 1 diabetes. Endocrinol Metab Clin North Am. 2010;39:513–25.PubMedCrossRefGoogle Scholar
  9. 9.
    Noble JA, Valdes AM, Cook M, Klitz W, Thomson G, Erlich HA. The role of HLA class II genes in insulin-dependent diabetes mellitus: molecular analysis of 180 Caucasian, multiplex families. Am J Hum Genet. 1996;59:1134–48.PubMedGoogle Scholar
  10. 10.
    Lambert AP, Gillespie KM, Thomson G, Cordell HJ, Todd JA, Gale EA, et al. Absolute risk of childhood-onset type 1 diabetes defined by human leukocyte antigen class II genotype: a population-based study in the United Kingdom. J Clin Endocrinol Metab. 2004;89:4037–43.PubMedCrossRefGoogle Scholar
  11. 11.
    Horton R, Wilming L, Rand V, Lovering RC, Bruford EA, Khodiyar VK, et al. Gene map of the extended human MHC. Nat Rev Genet. 2004;5:889–99.PubMedCrossRefGoogle Scholar
  12. 12.
    Thomson G, Valdes AM, Noble JA, Kockum I, Grote MN, Najman J, et al. Relative predispositional effects of HLA class II DRB1-DQB1 haplotypes and genotypes on type 1 diabetes: a meta-analysis. Tissue Antigens. 2007;70:110–27.PubMedCrossRefGoogle Scholar
  13. 13.
    Lander ES, Schork NJ. Genetic dissection of complex traits. Science. 1994;265:2037–48.PubMedCrossRefGoogle Scholar
  14. 14.
    Singal DP, Blajchman MA. Histocompatibility (HL-A) antigens, lymphocytotoxic antibodies and tissue antibodies in patients with diabetes mellitus. Diabetes. 1973;22:429–32.PubMedGoogle Scholar
  15. 15.
    Tait BD. Genetic susceptibility to type I diabetes: a review. J Autoimmun. 1990;3 Suppl 1:3–11.PubMedCrossRefGoogle Scholar
  16. 16.
    Payami H, Thomson G, Motro U, Louis EJ, Hudes E. The affected sib method. IV. Sib trios. Ann Hum Genet. 1985;49:303–14.PubMedCrossRefGoogle Scholar
  17. 17.
    Thomson G, Robinson WP, Kuhner MK, Joe S, MacDonald MJ, Gottschall JL, et al. Genetic heterogeneity, modes of inheritance, and risk estimates for a joint study of Caucasians with insulin-dependent diabetes mellitus. Am J Hum Genet. 1988;43:799–816.PubMedGoogle Scholar
  18. 18.
    •• Erlich H, Valdes AM, Noble J, Carlson JA, Varney M, Concannon P, Mychaleckyj JC, Todd JA, Bonella P, Fear AL, Lavant E, Louey A, Moonsamy P: HLA DR-DQ Haplotypes and Genotypes and Type 1 Diabetes Risk: Analysis of the Type 1 Diabetes Genetics Consortium Families. Diabetes 2008, 57:1084–1092. This paper summarizes the analyses of HLA class II DR- and DQ-encoding genes on T1D risk in the T1DGC samples. PubMedCrossRefGoogle Scholar
  19. 19.
    Robinson WP, Barbosa J, Rich SS, Thomson G. Homozygous parent affected sib pair method for detecting disease predisposing variants: application to insulin dependent diabetes mellitus. Genet Epidemiol. 1993;10:273–88.PubMedCrossRefGoogle Scholar
  20. 20.
    Nejentsev S, Howson JM, Walker NM, Szeszko J, Field SF, Stevens HE, et al. Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A. Nature. 2007;450:887–92.PubMedCrossRefGoogle Scholar
  21. 21.
    Thomson G. HLA DR antigens and susceptibility to insulin-dependent diabetes mellitus. Am J Hum Genet. 1984;36:1309–17.PubMedGoogle Scholar
  22. 22.
    Noble JA, Valdes AM, Bugawan TL, Apple RJ, Thomson G, Erlich HA. The HLA class I A locus affects susceptibility to type 1 diabetes. Hum Immunol. 2002;63:657–64.PubMedCrossRefGoogle Scholar
  23. 23.
    Svejgaard A, Ryder LP. HLA and insulin-dependent diabetes: an overview. Genet Epidemiol. 1989;6:1–14.PubMedCrossRefGoogle Scholar
  24. 24.
    Ronningen KS, Markussen G, Iwe T, Thorsby E. An increased risk of insulin-dependent diabetes mellitus (IDDM) among HLA-DR4, DQw8/DRw8, DQw4 heterozygotes. Hum Immunol. 1989;24:165–73.PubMedCrossRefGoogle Scholar
  25. 25.
    Valdes AM, Thomson G, Graham J, Zarghami M, McNeney B, Kockum I, et al. D6S265*15 marks a DRB1*15, DQB1*0602 haplotype associated with attenuated protection from type 1 diabetes mellitus. Diabetologia. 2005;48:2540–3.PubMedCrossRefGoogle Scholar
  26. 26.
    Pawelec G, Buhring HJ. Expression of MHC class II epitopes on human T lymphocyte clones. Cell Immunol. 1990;127:520–6.PubMedCrossRefGoogle Scholar
  27. 27.
    Cesbron A, Moreau P, Milpied N, Harousseau JL, Muller JY, Bignon JD. Crucial role of the third and fourth hypervariable regions of HLA-DPB1 allelic sequences in the mixed lymphocyte reaction. Hum Immunol. 1992;33:202–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Nicholson I, Varney M, Kanaan C, Grigg A, Szer J, Tiedemann K, et al. Alloresponses to HLA-DP detected in the primary MLR: correlation with a single amino acid difference. Hum Immunol. 1997;55:163–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Begovich AB, Bugawan TL, Nepom BS, Klitz W, Nepom GT, Erlich HA. A specific HLA-DP beta allele is associated with pauciarticular juvenile rheumatoid arthritis but not adult rheumatoid arthritis. Proc Natl Acad Sci U S A. 1989;86:9489–93.PubMedCrossRefGoogle Scholar
  30. 30.
    Rosenman KD, Rossman M, Hertzberg V, Reilly MJ, Rice C, Kanterakis E, et al. HLA class II DPB1 and DRB1 polymorphisms associated with genetic susceptibility to beryllium toxicity. Occup Environ Med. 2011;68:487–93.PubMedCrossRefGoogle Scholar
  31. 31.
    Cruz TD, Valdes AM, Santiago A, Frazer De Llado T, Raffel LJ, Zeidler A. DPB1 alleles are associated with type 1 diabetes susceptibility in multiple ethnic groups. Diabetes. 2004;53:2158–63.PubMedCrossRefGoogle Scholar
  32. 32.
    Al-Hussein KA, Rama NR, Ahmad M, Rozemuller E, Tilanus MG. HLA-DPB1*0401 is associated with dominant protection against type 1 diabetes in the general Saudi population and in subjects with a high-risk DR/DQ haplotype. Eur J Immunogenet. 2003;30:115–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Cucca F, Dudbridge F, Loddo M, Mulargia AP, Lampis R, Angius E, et al. The HLA-DPB1–associated component of the IDDM1 and its relationship to the major loci HLA-DQB1, -DQA1, and -DRB1. Diabetes. 2001;50:1200–5.PubMedCrossRefGoogle Scholar
  34. 34.
    Noble JA, Valdes AM, Thomson G, Erlich HA. The HLA class II locus DPB1 can influence susceptibility to type 1 diabetes. Diabetes. 2000;49:121–5.PubMedCrossRefGoogle Scholar
  35. 35.
    Nishimaki K, Kawamura T, Inada H, Yagawa K, Nose Y, Nabeya N, et al. HLA DPB1*0201 gene confers disease susceptibility in Japanese with childhood onset Type I diabetes, independent of HLA-DR and DQ genotypes. Diabetes Res Clin Pract. 2000;47:49–55.PubMedCrossRefGoogle Scholar
  36. 36.
    Erlich HA, Rotter JI, Chang JD, Shaw SD, Raffel LJ, Klitz W, et al. Association of HLA-DPB1*0301 with insulin dependent diabetes mellitus in Mexican-Americans. Diabetes. 1996;45:610–4.PubMedCrossRefGoogle Scholar
  37. 37.
    Balducci-Silano PL, Layrisse ZE. HLA-DP and susceptibility to insulin-dependent diabetes mellitus in an ethnically mixed population. Associations with other HLA-alleles. J Autoimmun. 1995;8:425–37.PubMedCrossRefGoogle Scholar
  38. 38.
    Baisch JM, Capra JD. Analysis of HLA genotypes and susceptibility to insulin-dependent diabetes mellitus: association maps telomeric to HLA-DP. Scand J Immunol. 1992;36:331–40.PubMedCrossRefGoogle Scholar
  39. 39.
    Johansson S, Lie BA, Pociot F, Nerup J, Cambon-Thomsen A, Kockum I, et al. HLA associations in type 1 diabetes: DPB1 alleles may act as markers of other HLA-complex susceptibility genes. Tissue Antigens. 2003;61:344–51.PubMedCrossRefGoogle Scholar
  40. 40.
    Lie BA, Akselsen HE, Joner G, Dahl-Jorgensen K, Ronningen KS, Thorsby E, et al. HLA associations in insulin-dependent diabetes mellitus: no independent association to particular DP genes. Hum Immunol. 1997;55:170–5.PubMedCrossRefGoogle Scholar
  41. 41.
    Mbanya JC, Sobngwi E, Mbanya DN. HLA-DRB1, -DQA1, -DQB1 and DPB1 susceptibility alleles in Cameroonian type 1 diabetes patients and controls. Eur J Immunogenet. 2001;28:459–62.PubMedCrossRefGoogle Scholar
  42. 42.
    • Varney MD, Valdes AM, Carlson JA, Noble JA, Tait BD, Bonella P, Lavant E, Fear AL, Louey A, Moonsamy P, Mychaleckyj JC, Erlich H: HLA DPA1, DPB1 alleles and haplotypes contribute to the risk associated with type 1 diabetes: analysis of the type 1 diabetes genetics consortium families. Diabetes 2010, 59:2055–2062. This paper summarizes the results of T1D association analyses of the HLA class II genes encoding the DP molecule in the T1DGC samples. PubMedCrossRefGoogle Scholar
  43. 43.
    Serreze DV, Holl TM, Marron MP, Graser RT, Johnson EA, Choisy-Rossi C, et al. MHC class II molecules play a role in the selection of autoreactive class I-restricted CD8 T cells that are essential contributors to type 1 diabetes development in nonobese diabetic mice. J Immunol. 2004;172:871–9.PubMedGoogle Scholar
  44. 44.
    Inoue K, Ikegami H, Fujisawa T, Noso S, Nojima K, Babaya N, et al. Allelic variation in class I K gene as candidate for a second component of MHC-linked susceptibility to type 1 diabetes in non-obese diabetic mice. Diabetologia. 2004;47:739–47.PubMedCrossRefGoogle Scholar
  45. 45.
    Nakanishi K, Kobayashi T, Murase T, Naruse T, Nose Y, Inoko H. Human leukocyte antigen-A24 and -DQA1*0301 in Japanese insulin-dependent diabetes mellitus: independent contributions to susceptibility to the disease and additive contributions to acceleration of beta-cell destruction. J Clin Endocrinol Metab. 1999;84:3721–5.PubMedCrossRefGoogle Scholar
  46. 46.
    •• Noble JA, Valdes AM, Varney MD, Carlson JA, Moonsamy P, Fear AL, Lane JA, Lavant E, Rappner R, Louey A, Concannon P, Mychaleckyj JC, Erlich HA: HLA class I and genetic susceptibility to type 1 diabetes: results from the Type 1 Diabetes Genetics Consortium. Diabetes 2010, 59:2972–2979. This paper describes the results of T1D association for HLA class I A, B, and C genes from the T1DGC samples. PubMedCrossRefGoogle Scholar
  47. 47.
    Valdes AM, Erlich HA, Noble JA. Human leukocyte antigen class I B and C loci contribute to Type 1 Diabetes (T1D) susceptibility and age at T1D onset. Hum Immunol. 2005;66:301–13.PubMedCrossRefGoogle Scholar
  48. 48.
    Baschal EE, Baker PR, Eyring KR, Siebert JC, Jasinski JM, Eisenbarth GS. The HLA-B*3906 allele imparts a high risk of diabetes only on specific HLA-DR/DQ haplotypes. Diabetologia. 2011;54:1702–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Cucca F, Lampis R, Frau F, Macis D, Angius E, Masile P, et al. The distribution of DR4 haplotypes in Sardinia suggests a primary association of type I diabetes with DRB1 and DQB1 loci. Hum Immunol. 1995;43:301–8.PubMedCrossRefGoogle Scholar
  50. 50.
    Cucca F, Muntoni F, Lampis R, Frau F, Argiolas L, Silvetti M, et al. Combinations of specific DRB1, DQA1, DQB1 haplotypes are associated with insulin-dependent diabetes mellitus in Sardinia. Hum Immunol. 1993;37:85–94.PubMedCrossRefGoogle Scholar
  51. 51.
    Hauptmann G, Bahram S. Genetics of the central MHC. Curr Opin Immunol. 2004;16:668–72.PubMedCrossRefGoogle Scholar
  52. 52.
    Johansson S, Lie BA, Todd JA, Pociot F, Nerup J, Cambon-Thomsen A, et al. Evidence of at least two type 1 diabetes susceptibility genes in the HLA complex distinct from HLA-DQB1, -DQA1 and -DRB1. Genes Immun. 2003;4:46–53.PubMedCrossRefGoogle Scholar
  53. 53.
    Noble JA, Valdes AM, Lane JA, Green AE, Erlich HA. Linkage disequilibrium with predisposing DR3 haplotypes accounts for apparent effects of tumor necrosis factor and lymphotoxin-alpha polymorphisms on type 1 diabetes susceptibility. Hum Immunol. 2006;67:999–1004.PubMedCrossRefGoogle Scholar
  54. 54.
    Eike MC, Olsson M, Undlien DE, Dahl-Jorgensen K, Joner G, Ronningen KS, et al. Genetic variants of the HLA-A, HLA-B and AIF1 loci show independent associations with type 1 diabetes in Norwegian families. Genes Immun. 2009;10:141–50.PubMedCrossRefGoogle Scholar
  55. 55.
    Valdes AM, Arden NK, Tamm A, Kisand K, Doherty S, Pola E, et al. A meta-analysis of interleukin-6 promoter polymorphisms on risk of hip and knee osteoarthritis. Osteoarthritis Cartilage. 2010;18:699–704.PubMedCrossRefGoogle Scholar
  56. 56.
    Roach JC, Deutsch K, Li S, Siegel AF, Bekris LM, Einhaus DC, et al. Genetic mapping at 3-kilobase resolution reveals inositol 1,4,5-triphosphate receptor 3 as a risk factor for type 1 diabetes in Sweden. Am J Hum Genet. 2006;79:614–27.PubMedCrossRefGoogle Scholar
  57. 57.
    Qu HQ, Marchand L, Szymborski A, Grabs R, Polychronakos C. The association between type 1 diabetes and the ITPR3 gene polymorphism due to linkage disequilibrium with HLA class II. Genes Immun. 2008;9:264–6.PubMedCrossRefGoogle Scholar
  58. 58.
    Aly TA, Baschal EE, Jahromi MM, Fernando MS, Babu SR, Fingerlin TE, et al. Analysis of single nucleotide polymorphisms identifies major type 1A diabetes locus telomeric of the major histocompatibility complex. Diabetes. 2008;57:770–6.PubMedCrossRefGoogle Scholar
  59. 59.
    Viken MK, Blomhoff A, Olsson M, Akselsen HE, Pociot F, Nerup J, et al. Reproducible association with type 1 diabetes in the extended class I region of the major histocompatibility complex. Genes Immun. 2009;10:323–33.PubMedCrossRefGoogle Scholar
  60. 60.
    Bossuyt P. In Evidence-based laboratory medicine: principles, practice, and outcomes Washington, DC, USA, AACC Press, 2007, p. 67–81.Google Scholar
  61. 61.
    Clayton DG. Prediction and interaction in complex disease genetics: experience in type 1 diabetes. PLoS Genet. 2009;5:e1000540.PubMedCrossRefGoogle Scholar
  62. 62.
    Aly TA, Ide A, Humphrey K, Barker JM, Steck A, Erlich HA, Yu L, Miao D, Redondo MJ, McFann K, Roberts CM, Babu SR, Norris JM, Eisenbarth GS, Rewers MJ: Genetic prediction of autoimmunity: initial oligogenic prediction of anti-islet autoimmunity amongst DR3/DR4-DQ8 relatives of patients with type 1A diabetes. J Autoimmun 25 2005, Suppl:40–45.Google Scholar
  63. 63.
    Aly TA, Ide A, Jahromi MM, Barker JM, Fernando MS, Babu SR, et al. Extreme genetic risk for type 1A diabetes. Proc Natl Acad Sci U S A. 2006;103:14074–9.PubMedCrossRefGoogle Scholar
  64. 64.
    Keymeulen B, Vandemeulebroucke E, Ziegler AG, Mathieu C, Kaufman L, Hale G, et al. Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N Engl J Med. 2005;352:2598–608.PubMedCrossRefGoogle Scholar
  65. 65.
    Cucca F, Lampis R, Congia M, Angius E, Nutland S, Bain SC, et al. 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;10:2025–37.PubMedCrossRefGoogle Scholar
  66. 66.
    Petrone A, Bugawan TL, Mesturino CA, Nistico L, Galgani A, Giorgi G, et al. The distribution of HLA class II susceptible/protective haplotypes could partially explain the low incidence of type 1 diabetes in continental Italy (Lazio region). Tissue Antigens. 2001;58:385–94.PubMedCrossRefGoogle Scholar
  67. 67.
    Pugliese A, Dorman JS, Steenkiste A. The 13th International Histocompatibility Working Group for Type 1 Diabetes (T1D) Joint Report. In: Hanson JA, editor. 13th International Histocompatibility Workshop and Conference. Seattle: IHWG Press; 2007. p. 788–96.Google Scholar
  68. 68.
    Hermann R, Turpeinen H, Laine AP, Veijola R, Knip M, Simell O, et al. HLA DR-DQ-encoded genetic determinants of childhood-onset type 1 diabetes in Finland: an analysis of 622 nuclear families. Tissue Antigens. 2003;62:162–9.PubMedCrossRefGoogle Scholar
  69. 69.
    Hermann R, Mijovic CH, Rayner M, Croft N, Kelly MA, Jenkins D, et al. HLA alleles and IDDM in children in Hungary: a comparison with Finland. Hum Immunol. 2001;62:391–8.PubMedCrossRefGoogle Scholar
  70. 70.
    Petrone A, Battelino T, Krzisnik C, Bugawan T, Erlich H, Di Mario U, et al. Similar incidence of type 1 diabetes in two ethnically different populations (Italy and Slovenia) is sustained by similar HLA susceptible/protective haplotype frequencies. Tissue Antigens. 2002;60:244–53.PubMedCrossRefGoogle Scholar
  71. 71.
    Saruhan-Direskeneli G, Uyar FA, Bas F, Gunoz H, Bundak R, Saka N, et al. HLA-DR and -DQ associations with insulin-dependent diabetes mellitus in a population of Turkey. Hum Immunol. 2000;61:296–302.PubMedCrossRefGoogle Scholar
  72. 72.
    Chang YW, Lam KS, Hawkins BR. Strong association between DQA1/DQB1 genotype and early-onset IDDM in Chinese: the association is with alleles rather than specific residues. Eur J Immunogenet. 1998;25:273–80.PubMedCrossRefGoogle Scholar
  73. 73.
    Chan SH, Thai AC, Lin YN, Liu KF, Wee GB. Influence of gender and age at onset on the HLA associations in Chinese with insulin-dependent diabetes mellitus. Hum Immunol. 1995;44:175–80.PubMedCrossRefGoogle Scholar
  74. 74.
    Bugawan TL, Klitz W, Alejandrino M, Ching J, Panelo A, Solfelix CM, et al. The association of specific HLA class I and II alleles with type 1 diabetes among Filipinos. Tissue Antigens. 2002;59:452–69.PubMedCrossRefGoogle Scholar
  75. 75.
    Erlich HA, Zeidler A, Chang J, Shaw S, Raffel LJ, Klitz W, et al. HLA class II alleles and susceptibility and resistance to insulin dependent diabetes mellitus in Mexican-American families. Nat Genet. 1993;3:358–64.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Children’s Hospital Oakland Research InstituteOaklandUSA
  2. 2.Department of Twin Research King’s College LondonLondonUK

Personalised recommendations