Immunogenetics of Type 1 Diabetes in Asian population: Immunogenetics of Type 1 Diabetes

Watip Tangjittipokin; Nipaporn Teerawattanapong; Thanida Tangjarusritaratorn

Authors

Watip Tangjittipokin
Nipaporn Teerawattanapong
Thanida Tangjarusritaratorn

Keywords:

Type 1 diabetes; Immunogenetics; Pathogenesis; Asia

Abstract

Type 1 diabetes (T1D) is an autoimmune disease. It is caused by a combination of genetic and environmental factors characterized by the destruction of the pancreatic β-cells and leading to multifactorial diseases for long term effects. It is the second most common chronic disease in children and accounts for 5% to 10% of all diagnosed cases of diabetes. More than 50 genetic risk regions contributing to the pathogenesis of T1D. The strongest genetics of T1D risk encodes on the classical human leukocyte antigens (HLA) on chromosome 6p21.31 estimated to account for 40-50%. Other genetic loci, non-HLA genes also contribute to T1D risk involving in both immune and non-immune genes. More information is needed to create predictive models for non-European populations. Comparative studies among different populations are needed to complete the knowledge base for the genetics of T1D risk to enable the eventual development of screening and intervention strategies applicable to all individuals, tailored to their genetic background. This review summarizes the current immunogenetics to the understanding of the pathogenesis of T1D emphasize on the Asian population.

References

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(2):115-9.

Allam G, Nasr A, Talaat IM, Abuelsaad ASA, Bakheit AM, Nemenqani D, Alsulaimani AA. Association between cytokine genes polymorphisms and type 1 diabetes: a case-control study on Saudi population. Immunol Invest. 2018;47(3):229-40.

Aminkeng F, Weets I, Van Autreve JE, Koeleman BPC, Quartier E, Van Schravendijk C, Gorus FK, Van der Auwera BJR. Association of IL-2RA/CD25 with type 1 diabetes in the Belgian population. Hum Immunol. 2010;71(12):1233-7.

Atkinson MA. The pathogenesis and natural history of type 1 diabetes. Cold Spring Harbor perspectives in medicine. 2012;2(11):a007641.

Awata T, Kawasaki E, Tanaka S, Ikegami H, Maruyama T, Shimada A, Nakanishi K, Kobayashi T, Iizuka H, Uga M. Association of type 1 diabetes with two Loci on 12q13 and 16p13 and the influence coexisting thyroid autoimmunity in Japanese. J Clin Endocrinol Metab. 2009;94(1):231-5.

Banchuin N, Boonyasrisawat W, Vannasaeng S, Dharakul T, Yenchitsomanus PT, Deerochanawong C, Ploybutr S, Sriussadaporn S, Pasurakul T. Cell-mediated immune responses to GAD and beta-casein in type 1 diabetes mellitus in Thailand. Diabetes Res Clin Pract. 2002;55(3):237-45.

Beyerlein A, Donnachie E, Jergens S, Ziegler AG. Infections in Early Life and Development of Type 1 Diabetes. Jama. 2016;315(17):1899-901.

Bingley PJ. Clinical applications of diabetes antibody testing. J Clin Endocrinol Metab. 2010;95(1):25-33.

Bjorkman PJ, Parham P. Structure, function, and diversity of class I major histocompatibility complex molecules. Annu Rev Biochem. 1990;59(1):253-88.

Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC. Structure of the human class I histocompatibility antigen, HLA-A2. Nature. 1987;329(6139):506-12.

Blanter M, Sork H, Tuomela S, Flodström-Tullberg M. Genetic and environmental interaction in type 1 diabetes: a relationship between genetic risk alleles and molecular traits of enterovirus infection? Curr Diab Rep. 2019;19(9):1-14.

Boonyasrisawat W, Banchuin N, Pattanapanyasat K, Deerochanawong C, Yenchitsomanus PT, Ploybutr S, Vannasaeng S. Flow cytometry for the analysis of T cells expressing CD69 after stimulation with glutamic acid decarboxylase. Asian Pac J Allergy Immunol. 2002;20(1):37-42.

Bugawan TL, Klitz W, Alejandrino M, Ching J, Panelo A, Solfelix CM, Petrone A, Buzzetti R, Pozzilli P, Erlich HA. The association of specific HLA class I and II alleles with type 1 diabetes among Filipinos. Tissue Antigens. 2002;59(6):452-69.

Burrack AL, Martinov T, Fife BT. T cell-mediated beta cell destruction: autoimmunity and alloimmunity in the context of type 1 diabetes. Front Endocrinol. 2017;8:343.

Buzzetti R, Tuomi T, Mauricio D, Pietropaolo M, Zhou Z, Pozzilli P, Leslie RD. Management of latent autoimmune diabetes in adults: a consensus statement from an international expert panel. Diabetes. 2020;69(10):2037-47.

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(3):175-80.

Chandanayingyong D, Stephens HAF, Fan L, Sirikong M, Longta P, Vangseratthana R, Lekmak S, Longta K, Bejrachandra S, Rungruang E. HLA-DPB1 polymorphism in the Thais of Southeast Asia. Hum Immunol. 1994;40(1):20-4.

Chang YW, Lam KSL, 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(4):273-80.

Chiasson J-L, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M, Group S-NTR. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet. 2002;359(9323):2072-7.

Chistiakov DA, Voronova NV, Savost'Anov KV, Turakulov RI. Loss-of-function mutations E6 27X and I923V of IFIH1 are associated with lower poly(I:C)-induced interferon-β production in peripheral blood mononuclear cells of type 1 diabetes patients. Hum Immunol. 2010;71(11):1128-34.

Choo SY. The HLA system: genetics, immunology, clinical testing, and clinical implications. Yonsei Med J. 2007;48(1):11-23.

Chung HR, Yang SW, Shin CH, Park KS, Lee YA, Kim JH, Lee SH, Kim JH. The association of variable number of tandem repeats of the insulin gene with susceptibility to type 1 diabetes among Korean subjects. Diabetes Metab Res Rev. 2010;26(6):474-80.

Cinek O, Stene LC, Kramna L, Tapia G, Oikarinen S, Witsø E, Rasmussen T, Torjesen PA, Hyöty H, Rønningen KS. Enterovirus RNA in longitudinal blood samples and risk of islet autoimmunity in children with a high genetic risk of type 1 diabetes: the MIDIA study. Diabetologia. 2014;57(10):2193-200.

Coppieters KT, Wiberg A, Tracy SM, von Herrath MG. Immunology in the clinic review series: focus on type 1 diabetes and viruses: the role of viruses in type 1 diabetes: a difficult dilemma. Clin Exp Immunol. 2012;168(1):5-11.

Das SN, Baniasadi V, Kapuria V. Association of -308 TNF-α promoter polymorphism with type 1 diabetes in North Indians. Int J Immunogenet. 2006;33(6):411-6.

Eerligh P, Koeleman B, Dudbridge F, Jan Bruining G, Roep B, Giphart M. Functional genetic polymorphisms in cytokines and metabolic genes as additional genetic markers for susceptibility to develop type 1 diabetes. Genes Immun. 2004;5(1):36-40.

Espino-Paisan L, de la Calle H, Fernandez-Arquero M, Figueredo MA, de la Concha EG, Urcelay E, Santiago JL. A polymorphism in PTPN2 gene is associated with an earlier onset of type 1 diabetes. Immunogenetics. 2011;63(4):255-8.

Esposito S, Toni G, Tascini G, Santi E, Berioli MG, Principi N. Environmental factors associated with type 1 diabetes. Front Endocrinol. 2019;10:592.

Felner EI, Klitz W, Ham M, Lazaro AM, Stastny P, Dupont B, White PC. Genetic interaction among three genomic regions creates distinct contributions to early-and late-onset type 1 diabetes mellitus. Pediatr Diabetes. 2005;6(4):213-20.

Forbes JM, Söderlund J, Yap FYT, Knip M, Andrikopoulos S, Ilonen J, Simell O, Veijola R, Sourris KC, Coughlan MT, et al. Receptor for advanced glycation end-products (RAGE) provides a link between genetic susceptibility and environmental factors in type 1 diabetes. Diabetologia. 2011;54(5):1032-42.

Forrest JM, Menser MA, Burgess JA. High frequency of diabetes mellitus in young adults with congenital rubella. Lancet. 1971;2(7720):332-4.

Group DP. Incidence and trends of childhood Type 1 diabetes worldwide 1990–1999. Diabet Med. 2006;23(8):857-66.

Guberski D, Thomas V, Shek W, Like A, Handler E, Rossini A, Wallace J, Welsh R. Induction of type I diabetes by Kilham's rat virus in diabetes-resistant BB/Wor rats. Science. 1991;254(5034):1010-3.

Harrison JW, Tallapragada DSP, Baptist A, Sharp SA, Bhaskar S, Jog KS, Patel KA, Weedon MN, Chandak GR, Yajnik CS. Type 1 diabetes genetic risk score is discriminative of diabetes in non-Europeans: evidence from a study in India. Sci Reps. 2020;10(1):1-7.

Hirsch D, Narinski R, Klein T, Israel S, Singer J. Immunogenetics of HLA class II in Israeli patients with adult-onset type 1 diabetes mellitus. Hum Immunol. 2007;68(7):616-22.

Honeyman MC, Coulson BS, Stone NL, Gellert SA, Goldwater PN, Steele CE, Couper JJ, Tait BD, Colman PG, Harrison LC. Association between rotavirus infection and pancreatic islet autoimmunity in children at risk of developing type 1 diabetes. Diabetes. 2000;49(8):1319-24.

Hsu WC, Okeke E, Cheung S, Keenan H, Tsui T, Cheng K, King GL. A cross-sectional characterization of insulin resistance by phenotype and insulin clamp in East Asian Americans with type 1 and type 2 diabetes. PloS one. 2011;6(12):e28311.

Hyöty H, Leinikki P, Reunanen A, Ilonen J, Surcel HM, Rilva A, Käär ML, Huupponen T, Hakulinen A, Mäkelä AL, et al. Mumps infections in the etiology of type 1 (insulin-dependent) diabetes. Diabetes Res. 1988;9(3):111-6.

Hyöty H, Taylor KW. The role of viruses in human diabetes. Diabetologia. 2002;45(10):1353-61.

Ikegami H, Noso S, Babaya N, Hiromine Y, Kawabata Y. Genetic Basis of Type 1 Diabetes: Similarities and Differences between East and West. The review of diabetic studies : RDS. 2008;5(2):64-72.

Ilonen J, Lempainen J, Hammais A, Laine AP, Härkönen T, Toppari J, Veijola R, Knip M. Primary islet autoantibody at initial seroconversion and autoantibodies at diagnosis of type 1 diabetes as markers of disease heterogeneity. Pediatr Diabetes. 2018;19(2):284-92.

Inshaw JR, Cutler AJ, Burren OS, Stefana MI, Todd JA. Approaches and advances in the genetic causes of autoimmune disease and their implications. Nat Immunol. 2018;19(7):674-84.

Jaya R, Zettyana Y, Bakri A, Yuwono Y, Aditiawati A. Polymorphisms associated with type 1 diabetes mellitus. Paediatr Indones. 2018;58(6):274-9.

Jermendy A, Szatmári I, Laine AP, Lukács K, Horváth KH, Körner A, Madácsy L, Veijola R, Simell O, Knip M, et al. The interferon-induced helicase IFIH1 Ala946Thr polymorphism is associated with type 1 diabetes in both the high-incidence Finnish and the medium-incidence Hungarian populations. Diabetologia. 2010;53(1):98-102.

Jung MH, Suh BK, Kim TG, Shin CH, Lee BC. Association of HLA class II and non-HLA gene polymorphisms with disease susceptibility in Korean children with type 1 diabetes mellitus. Journal of Korean Society of Pediatric Endocrinology. 2004;9(2):136-44.

Kahles H, Fain PR, Baker P, Eisenbarth G, Badenhoop K. Genetics of Autoimmune Thyroiditis in Type 1 Diabetes Reveals a Novel Association With DPB1*0201: Data From the Type 1 Diabetes Genetics Consortium. Diabetes care. 2015;38 Suppl 2:S21-8.

Kanga U, Vaidyanathan B, Jaini R, Menon PSN, Mehra NK. HLA haplotypes associated with type 1 diabetes mellitus in North Indian children. Hum Immunol. 2004;65(1):47-53.

Kaprio J, Tuomilehto J, Koskenvuo M, Romanov K, Reunanen A, Eriksson J, Stengård J, Kesäniemi YA. Concordance for type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus in a population-based cohort of twins in Finland. Diabetologia. 1992;35(11):1060-7.

Karvonen M, Jäntti V, Muntoni S, Stabilini M, Stabilini L, Muntoni S, Tuomilehto J. Comparison of the seasonal pattern in the clinical onset of IDDM in Finland and Sardinia. Diabetes care. 1998;21(7):1101-9.

Kaufman DL, Erlander MG, Clare-Salzler M, Atkinson MA, Maclaren NK, Tobin AJ. Autoimmunity to two forms of glutamate decarboxylase in insulin-dependent diabetes mellitus. J Clin Invest. 1992;89(1):283-92.

Kavvoura FK, Ioannidis JPA. Ala45Thr polymorphism of the NEUROD1 gene and diabetes susceptibility: a meta-analysis. Hum Genet. 2005;116(3):192-9.

Kawabata Y, Ikegami H, Kawaguchi Y, Fujisawa T, Shintani M, Ono M, Nishino M, Uchigata Y, Lee I, Ogihara T. Asian-specific HLA haplotypes reveal heterogeneity of the contribution of HLA-DR and -DQ haplotypes to susceptibility to type 1 diabetes. Diabetes. 2002;51(2):545.

Kawasaki E. Type 1 diabetes and autoimmunity. Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology. 2014;23(4):99-105.

Kiani J, Hajilooi M, Furst D, Rezaei H, Shahryari-Hesami S, Kowsarifard S, Zamani A, Solgi G. HLA class II susceptibility pattern for type 1 diabetes (T1D) in an Iranian population. Int J Immunogenet. 2015;42(4):279-86.

Klitz W, Bugawan TL, Panelo A, Solfelix CM, Buzzetti R, Pozzilli P, Steiner L, Alejandrino M, Erlich HA. Association of CTLA-4 variation with type I diabetes in Filipinos. Immunogenetics. 2002;54(5):310-3.

Knip M, Siljander H. Autoimmune mechanisms in type 1 diabetes. Autoimmun Rev. 2008;7(7):550-7.

Knip M, Veijola R, Virtanen SM, Hyöty H, Vaarala O, Akerblom HK. Environmental triggers and determinants of type 1 diabetes. Diabetes. 2005;54 Suppl 2:S125-36.

Koskinen MK, Mikk ML, Laine AP, Lempainen J, Löyttyniemi E, Vähäsalo P, Hekkala A, Härkönen T, Kiviniemi M, Simell O, et al. Longitudinal pattern of first-phase insulin response is associated with genetic variants outside the class II HLA region in children with multiple autoantibodies. Diabetes. 2020;69(1):12-9.

Kostraba JN, Cruickshanks KJ, Lawler-Heavner J, Jobim LF, Rewers MJ, Gay EC, Chase HP, Klingensmith G, Hamman RF. Early exposure to cow's milk and solid foods in infancy, genetic predisposition, and risk of IDDM. Diabetes. 1993;42(2):288-95.

Krischer JP, Lynch KF, Lernmark Å, Hagopian WA, Rewers MJ, She J-X, Toppari J, Ziegler A-G, Akolkar B, Group TS. Genetic and environmental interactions modify the risk of diabetes-related autoimmunity by 6 years of age: the TEDDY study. Diabetes care. 2017;40(9):1194-202.

Kumar N, Kaur G, Kanga U, Mehra NK, Neolia SC, Tandon N, Zucman SC. CTLA4+49G allele associates with early onset of type 1 diabetes in North Indians. Int J Immunogenet. 2015;42(6):445-52.

Kumar N, Kaur G, Kanga U, Tandon N, Caillat-Zucman S, Mehra NK. Association of PTPN22+1858C/T polymorphism with Type 1 diabetes in the North Indian population. Int J Immunogenet. 2014;41(4):318-23.

Kumar N, Mehra NK, Kanga U, Kaur G, Tandon N, Chuzho N, Mishra G, Neolia SC. Diverse human leukocyte antigen association of type 1 diabetes in north India. J Diabetes. 2019;11(9):719-28.

Laitinen OH, Honkanen H, Pakkanen O, Oikarinen S, Hankaniemi MM, Huhtala H, Ruokoranta T, Lecouturier V, André P, Harju R, et al. Coxsackievirus B1 is associated with induction of β-cell autoimmunity that portends type 1 diabetes. Diabetes. 2014;63(2):446-55.

Lamb MM, Yin X, Barriga K, Hoffman MR, Barón AE, Eisenbarth GS, Rewers M, Norris JM. Dietary glycemic index, development of islet autoimmunity, and subsequent progression to type 1 diabetes in young children. J Clin Endocrinol Metab. 2008;93(10):3936-42.

Lempainen J, Harkonen T, Laine A, Knip M, Ilonen J. Associations of polymorphisms in non-HLA loci with autoantibodies at the diagnosis of type 1 diabetes: INS and IKZF4 associate with insulin autoantibodies. Pediatr Diabetes. 2013;14(7):490-6.

Lempainen J, Laine AP, Hammais A, Toppari J, Simell O, Veijola R, Knip M, Ilonen J. Non-HLA gene effects on the disease process of type 1 diabetes: From HLA susceptibility to overt disease. J Autoimmun. 2015;61:45-53.

Lempainen J, Vaarala O, Mäkelä M, Veijola R, Simell O, Knip M, Hermann R, Ilonen J. Interplay between PTPN22 C1858T polymorphism and cow's milk formula exposure in type 1 diabetes. J Autoimmun. 2009;33(2):155-64.

Li M, Song LJ, Qin XY. Advances in the cellular immunological pathogenesis of type 1 diabetes. Journal of cellular and molecular medicine. 2014;18(5):749-58.

Likitmaskul S, Wacharasindhu S, Rawdaree P, Ngarmukos C, Deerochanawong C, Suwanwalaikorn S, Chetthakul T, Bunnag P, Kosachunhanun N, Plengvidhaya N, et al. Thailand diabetes registry project: type of diabetes, glycemic control and prevalence of microvascular complications in children and adolescents with diabetes. J Med Assoc Thai. 2006;89 Suppl 1:S10-6.

Lipponen K, Gombos Z, Kiviniemi M, Siljander H, Lempainen J, Hermann R, Veijola R, Simell O, Knip M, Ilonen J. Effect of HLA class I and class II alleles on progression from autoantibody positivity to overt type 1 diabetes in children with risk-associated class II genotypes. Diabetes. 2010;59(12):3253-6.

Liu E, Eisenbarth GS. Type 1A diabetes mellitus-associated autoimmunity. Endocrinol Metab Clin North Am. 2002;31(2):391-410, vii-viii.

Liu LL, Yi JP, Beyer J, Mayer-Davis EJ, Dolan LM, Dabelea DM, Lawrence JM, Rodriguez BL, Marcovina SM, Waitzfelder BE, et al. Type 1 and Type 2 Diabetes in Asian and Pacific Islander U.S. Youth. Diabetes care. 2009;32(Supplement 2):S133.

Lühder F, Schlosser M, Mauch L, Haubruck H, Rjasanowski I, Michaelis D, Kohnert KD, Ziegler M. Autoantibodies against GAD65 rather than GAD67 precede the onset of type 1 diabetes. Autoimmunity. 1994;19(2):71-80.

Luo S, Lin J, Xie Z, Xiang Y, Zheng P, Huang G, Li X, Liao Y, Hagopian WA, Wang CY, et al. HLA Genetic Discrepancy Between Latent Autoimmune Diabetes in Adults and Type 1 Diabetes: LADA China Study No. 6. J Clin Endocrinol Metab. 2016;101(4):1693-700.

Manan H, Angham AM, Sitelbanat A. Genetic and diabetic auto-antibody markers in Saudi children with type 1 diabetes. Hum Immunol. 2010;71(12):1238-42.

Mazumder R, Sarkar D, Chowdhury BR, Chowdhury UR, Chowdhury S. Clinical assessment of obesity and insulin resistance in type 1 diabetes subjects seen at a center in Kolkata. J Assoc Physicians India. 2009;57:511-4.

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

Mikk ML, Heikkinen T, El-Amir MI, Kiviniemi M, Laine AP, Härkönen T, Veijola R, Toppari J, Knip M, Ilonen J, et al. The association of the HLA-A*24:02, B*39:01 and B*39:06 alleles with type 1 diabetes is restricted to specific HLA-DR/DQ haplotypes in Finns. HLA. 2017;89(4):215-24.

Mikk ML, Kiviniemi M, Laine AP, Härkönen T, Veijola R, Simell O, Knip M, Ilonen J. The HLA-B*39 allele increases type 1 diabetes risk conferred by HLA-DRB1*04:04-DQB1*03:02 and HLA-DRB1*08-DQB1*04 class II haplotypes. Hum Immunol. 2014;75(1):65-70.

Mrena S, Virtanen S, Laippala P, Kulmala P, Hannila M-L, Akerblom H, Knip M. Models for Predicting Type 1 Diabetes in Siblings of Affected Children. Diabetes care. 2006;29:662-7.

Noble JA, Valdes AM, Varney MD, Carlson JA, Moonsamy P, Fear AL, Lane JA, Lavant E, Rappner R, Louey A, et al. HLA class I and genetic susceptibility to type 1 diabetes: Results from the type 1 diabetes genetics consortium. Diabetes. 2010;59(11):2972-9.

Orozco G, Eerligh P, Sánchez E, Zhernakova S, Roep BO, González-Gay MA, López-Nevot MA, Callejas JL, Hidalgo C, Pascual-Salcedo D, et al. Analysis of a functional BTNL2 polymorphism in type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus. Hum Immunol. 2005;66(12):1235-41.

Park Y. Why is type 1 diabetes uncommon in Asia? Ann N Y Acad Sci. 2006;1079(1):31-40.

Park Y, Kim S, Park S, Kim T, Yu L, Rewers M, Eisenbarth GS. Differential expression of nonislet autoimmunity: comparison of Korean and U.S. patients with type 1 diabetes. Ann N Y Acad Sci. 2004;1037:69-73.

Parkkola A, Laine AP, Karhunen M, Härkönen T, Ryhänen SJ, Ilonen J, Knip M, Groop PH, Ilonen J, Lappi A, et al. HLA and non-HLA genes and familial predisposition to autoimmune diseases in families with a child affected by type 1 diabetes. PloS one. 2017;12(11).

Patterson C, Guariguata L, Dahlquist G, Soltész G, Ogle G, Silink M. Diabetes in the young - a global view and worldwide estimates of numbers of children with type 1 diabetes. Diabetes Res Clin Pract. 2014;103(2):161-75.

Patterson CC, Karuranga S, Salpea P, Saeedi P, Dahlquist G, Soltesz G, Ogle GD. Worldwide estimates of incidence, prevalence and mortality of type 1 diabetes in children and adolescents: Results from the International Diabetes Federation Diabetes Atlas. Diabetes Res Clin Pract. 2019;157:107842.

Perez-Bravo F, Carrasco E, Gutierrez-Lopez M, Martinez M, Lopez G, de los Rios MG. Genetic predisposition and environmental factors leading to the development of insulin-dependent diabetes mellitus in Chilean children. J Mol Med. 1996;74(2):105-9.

Pihoker C, Gilliam LK, Hampe CS, Lernmark A. Autoantibodies in diabetes. Diabetes. 2005;54 Suppl 2:S52-61.

Pociot F, Lernmark Å. Genetic risk factors for type 1 diabetes. Lancet. 2016;387(10035):2331-9.

Principi N, Berioli MG, Bianchini S, Esposito S. Type 1 diabetes and viral infections: What is the relationship? J Clin Virol. 2017;96:26-31.

Pugliese A. Autoreactive T cells in type 1 diabetes. J Clin Invest. 2017;127(8):2881-91.

Ramachandran A, Snehalatha C, Ma RC. Diabetes in South-East Asia: an update. Diabetes Res Clin Pract. 2014;103(2):231-7.

Rewers M, Ludvigsson J. Environmental risk factors for type 1 diabetes. Lancet 2016;387(10035):2340-8.

Russell JT, Roesch LFW, Ördberg M, Ilonen J, Atkinson MA, Schatz DA, Triplett EW, Ludvigsson J. Genetic risk for autoimmunity is associated with distinct changes in the human gut microbiome. Nat Commun. 2019;10(1):3621.

Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, Colagiuri S, Guariguata L, Motala AA, Ogurtsova K. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas. Diabetes Res Clin Pract. 2019;157:107843.

Schweiger DS, Mendez A, Jamnik SK, Bratanic N, Bratina N, Battelino T, Brecelj J, Vidan-Jeras B. Genetic risk for co-occurrence of type 1 diabetes and celiac disease is modified by HLA-C and killer-immunoglobulin like receptors. Tissue Antigens. 2015;85(5):329.

Sharma A, Liu X, Hadley D, Hagopian W, Chen W-M, Onengut-Gumuscu S, Törn C, Steck AK, Frohnert BI, Rewers M. Identification of non-HLA genes associated with development of islet autoimmunity and type 1 diabetes in the prospective TEDDY cohort. J Autoimmun. 2018;89:90-100.

Sidney J, Schloss J, Moore C, Lindvall M, Wriston A, Hunt DF, Shabanowitz J, DiLorenzo TP, Sette A. Characterization of the peptide binding specificity of the HLA class I alleles B*38:01 and B*39:06. Immunogenetics. 2016;68(3):231-6.

Singal DP, Blajchman MA. Histocompatibility (HL-A) antigens, lymphocytotoxic antibodies and tissue antibodies in patients with diabetes mellitus. Diabetes. 1973;22(6):429-32.

Sloboda C, Vedran B, Roberto M. MECHANISMS IN ENDOCRINOLOGY: Insulin and type 1 diabetes: immune connections. Eur J Endocrinol. 2013;168(2):R19-R31.

Snell-Bergeon JK, Smith J, Dong F, Barón AE, Barriga K, Norris JM, Rewers M. Early childhood infections and the risk of islet autoimmunity: the Diabetes Autoimmunity Study in the Young (DAISY). Diabetes care. 2012;35(12):2553-8.

Song GG, Choi SJ, Ji JD, Lee YH. Association between the SUMO4 M55V (A163G) polymorphism and susceptibility to type 1 diabetes: A meta-analysis. Hum Immunol. 2012;73(10):1055-9.

Steck AK, Rewers MJ. Genetics of type 1 diabetes. Clin Chem. 2011;57(2):176-85.

Sun C, Sedimbi SK, Ashok AK, Sanjeevi CB, Lernmark Å, Landin-Olsson M, Kockum I, Arnqvist H, Björck E, Eriksson J, et al. CRYAB-650 C>G (rs2234702) affects susceptibility to Type 1 diabetes and IAA-positivity in Swedish population. Hum Immunol. 2012;73(7):759-66.

Tang X, Yan X, Zhou H, Yang X, Niu X, Liu J, Ji Q, Ji L, Li X, Zhou Z. Prevalence and identification of type 1 diabetes in Chinese adults with newly diagnosed diabetes. Diabetes Metab Syndr Obes. 2019;12:1527.

Taniyama M, Maruyama T, Tozaki T, Nakano Y, Ban Y. Association of PTPN22 haplotypes with type 1 diabetes in the Japanese population. Hum Immunol. 2010;71(8):795-8.

Tantawy AAG. Immunogenetics of type 1 diabetes mellitus. Egypt J Pediatr Allergy Immunol 2008;6(1):3-12.

Taplin CE, Barker JM. Autoantibodies in type 1 diabetes. Autoimmunity. 2008;41(1):11-8.

Thammarakcharoen T, Hirankarn N, Sahakitrungruang T, Thongmee T, Kuptawintu P, Kanoonthong S, Chongsrisawat V. Frequency of HLA-DQB1*0201/02 and DQB1*0302 alleles and tissue transglutaminase antibody seropositivity in children with type 1 diabetes mellitus. Asian Pac J Allergy Immunol. 2017;35(2):82-5.

Tuchinda C, Likitmaskul S, Unachak K, Panamonta O, Patarakijavanich N, Chetthakul T. The epidemiology of type 1 diabetes in Thai children. J Med Assoc Thai. 2002;85(6):648-52.

Tung YC, Fann CS, Chang CC, Chu CC, Yang WS, Hwu WL, Chen PL, Tsai WY. Comprehensive human leukocyte antigen genotyping of patients with type 1 diabetes mellitus in Taiwan. Pediatr Diabetes. 2018;19(4):699-706.

Turunen JA, Wessman M, Forsblom C, Kilpikari R, Parkkonen M, Pöntynen N, Ilmarinen T, Ulmanen I, Peltonen L, Groop PH. Association analysis of the AIRE and insulin genes in Finnish type 1 diabetic patients. Immunogenetics. 2006;58(5-6):331-8.

Valdes AM, Erlich HA, Carlson J, Varney M, Moonsamy PV, Noble JA. Use of class i and class II HLA loci for predicting age at onset of type 1 diabetes in multiple populations. Diabetologia. 2012;55(9):2394-401.

Van Autreve JE, Weets I, Gulbis B, Vertongen F, Gorus FK, Van der Auwera BJ, Registry BD. The rare HLA-DQA1* 03-DQB1* 02 haplotype confers susceptibility to type 1 diabetes in whites and is preferentially associated with early clinical disease onset in male subjects. Hum Immunol. 2004;65(7):729-36.

Vatanen T, Franzosa EA, Schwager R, Tripathi S, Arthur TD, Vehik K, Lernmark Å, Hagopian WA, Rewers MJ, She J-X. The human gut microbiome in early-onset type 1 diabetes from the TEDDY study. Nature. 2018;562(7728):589-94.

Virtanen SM, Läärä E, Hyppönen E, Reijonen H, Räsänen L, Aro A, Knip M, Ilonen J, Akerblom HK. Cow's milk consumption, HLA-DQB1 genotype, and type 1 diabetes: a nested case-control study of siblings of children with diabetes. Childhood diabetes in Finland study group. Diabetes. 2000;49(6):912-7.

Viskari H, Knip M, Tauriainen S, Huhtala H, Veijola R, Ilonen J, Simell O, Surcel HM, Hyöty H. Maternal enterovirus infection as a risk factor for type 1 diabetes in the exposed offspring. Diabetes care. 2012;35(6):1328-32.

Wagenknecht LE, Roseman JM, Herman WH. Increased incidence of insulin-dependent diabetes mellitus following an epidemic of Coxsackievirus B5. Am J Epidemiol. 1991;133(10):1024-31.

Wang G, Zhang Q, Xu N, Xu K, Wang J, He W, Yang T. Associations between Two Polymorphisms (FokI and BsmI) of Vitamin D Receptor Gene and Type 1 Diabetes Mellitus in Asian Population: A Meta-Analysis. PloS one. 2014;9(3):e89325.

Weng J, Zhou Z, Guo L, Zhu D, Ji L, Luo X, Mu Y, Jia W. Incidence of type 1 diabetes in China, 2010-13: population based study. BMJ (Clinical research ed.). 2018;360.

Wenzlau JM, Hutton JC. Novel diabetes autoantibodies and prediction of type 1 diabetes. Curr Diab Rep. 2013;13(5):608-15.

Wenzlau JM, Juhl K, Yu L, Moua O, Sarkar SA, Gottlieb P, Rewers M, Eisenbarth GS, Jensen J,

Davidson HW, et al. The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proc Natl Acad Sci U S A. 2007;104(43):17040-5.

White NH. Diabetic ketoacidosis in children. Endocrinol Metab Clin North Am. 2000;29(4):657-82.

Winter WE, Schatz DA. Autoimmune markers in diabetes. Clin Chem. 2011;57(2):168-75.

Xie Z, Chang C, Zhou Z. Molecular mechanisms in autoimmune type 1 diabetes: a critical review. Clin Rev Allergy Immunol. 2014;47(2):174-92.

Yeo L, Pujol-Autonell I, Baptista R, Eichmann M, Kronenberg-Versteeg D, Heck S, Dolton G, Sewell AK, Härkönen T, Mikk M-L. Circulating β cell-specific CD8+ T cells restricted by high-risk HLA class I molecules show antigen experience in children with and at risk of type 1 diabetes. Clin Exp Immunol. 2020;199(3):263-77.

Yu L, Miao D, Scrimgeour L, Johnson K, Rewers M, Eisenbarth GS. Distinguishing persistent insulin autoantibodies with differential risk: nonradioactive bivalent proinsulin/insulin autoantibody assay. Diabetes. 2012;61(1):179-86.

Zhou Z, Xiang Y, Ji L, Jia W, Ning G, Huang G, Yang L, Lin J, Liu Z, Hagopian WA, et al. Frequency, immunogenetics, and clinical characteristics of latent autoimmune diabetes in China (LADA China Study): A nationwide, multicenter, clinic-based cross-sectional study. Diabetes. 2013;62(2):543-50.

Zung A, Elizur M, Weintrob N, Bistritzer T, Hanukoglu A, Zadik Z, Phillip M, Miller K, Koren I, Brautbar C, et al. Type 1 diabetes in Jewish Ethiopian immigrants in Israel: HLA class II immunogenetics and contribution of new environment. Hum Immunol. 2004;65(12):1463-8.

Immunogenetics of Type 1 Diabetes in Asian population