Type I diabetes mellitus

The majority of type 1 diabetes mellitus (T1DM) cases are believed to arise from an inflammatory, autoimmune attack against the beta cells in the pancreas, which consequently leads to the failure of insulin-mediated blood glucose regulation in the body. T1DM signs and symptoms can come on quickly and may include increased thirst and frequent urination, fatigue, weight loss and so on. It is recognized that both genetic and environmental determinants are important in defining disease risk. The HLA class II genes are most strongly associated with T1DM. Another plausible candidate genes are INS, CTLA4 and PTPN22. The disease may be a result of variations in several susceptibility genes, with the majority only contributing weak effects.

Metabolic disease; Immune system disease; Endocrine system disease

HLA-DRB1 (polymorphism) [HSA:3123] [KO:K06752]
HLA-DQB1 (polymorphism) [HSA:3119] [KO:K06752]
HLA-DQA1 (polymorphism) [HSA:3117] [KO:K06752]
INS (polymorphism) [HSA:3630] [KO:K04526]
CTLA-4 (polymorphism) [HSA:1493] [KO:K06538]
PTPN22 (polymorphism) [HSA:26191] [KO:K01104]
IL-2RA (polymorphism) [HSA:3559] [KO:K05068]
PTPN2 (polymorphism) [HSA:5771] [KO:K01104]
ERBB3 (polymorphism) [HSA:2065] [KO:K05084]
IL2 - IL21 (intergenic region polymorphism) [HSA:3558 59067] [KO:K05429 K05434]
IFIH1 (polymorphism) [HSA:64135] [KO:K12647]
CLEC16A (polymorphism) [HSA:23274]
BACH2 (polymorphism) [HSA:60468] [KO:K09042]
PRKCQ (polymorphism) [HSA:5588] [KO:K06068]
CTSH (polymorphism) [HSA:1512] [KO:K01366]
C1QTNF6 (polymorphism) [HSA:114904]
SH2B3 (polymorphism) [HSA:10019] [KO:K12459]
C12orf30 (polymorphism) [HSA:80018]
CD226 (polymorphism) [HSA:10666] [KO:K06567]
ITPR3 (polymorphism) [HSA:3710] [KO:K04960]
CYP27B1 (polymorphism) [HSA:1594] [KO:K07438]

Enterovirus (polioviruses, coxsackievirus B serotypes)
Congenital rubella infection
Cow's milk proteins
Deficiency of vitamin D
N-Nitroso compounds

GAD65
IA2-Ab
IAA
ICA

Insulin [DR:D00085]

PMID:19369670 (gene)

Concannon P, Rich SS, Nepom GT

Genetics of type 1A diabetes.

N Engl J Med 360:1646-54 (2009)

PMID:18482868 (gene)

Ounissi-Benkalha H, Polychronakos C

The molecular genetics of type 1 diabetes: new genes and emerging mechanisms.

Trends Mol Med 14:268-75 (2008)

PMID:19232167 (gene)

Bergholdt R

Understanding type 1 diabetes genetics - approaches for identification of susceptibility genes in multi-factorial diseases.

Dan Med Bull 56:1-39 (2009)

PMID:19884899 (gene)

Handel AE, Handunnetthi L, Ebers GC, Ramagopalan SV

Type 1 diabetes mellitus and multiple sclerosis: common etiological features.

Nat Rev Endocrinol 5:655-64 (2009)

PMID:17554260

Todd JA, Walker NM, Cooper JD, Smyth DJ, Downes K, Plagnol V, Bailey R, Nejentsev S, Field SF, Payne F, Lowe CE, Szeszko JS, Hafler JP, Zeitels L, Yang JH, Vella A, Nutland S, Stevens HE, Schuilenburg H, Coleman G, Maisuria M, Meadows W, Smink LJ, Healy B, Burren OS, Lam AA, Ovington NR, Allen J, Adlem E, Leung HT, Wallace C, Howson JM, Guja C, Ionescu-Tirgoviste C, Simmonds MJ, Heward JM, Gough SC, Dunger DB, Wicker LS, Clayton DG

Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes.

Nat Genet 39:857-64 (2007)

PMID:18978792 (gene)

Cooper JD, Smyth DJ, Smiles AM, Plagnol V, Walker NM, Allen JE, Downes K, Barrett JC, Healy BC, Mychaleckyj JC, Warram JH, Todd JA

Meta-analysis of genome-wide association study data identifies additional type 1  diabetes risk loci.

Nat Genet 40:1399-401 (2008)

PMID:16475896 (marker)

Seissler J, Scherbaum WA

Autoimmune diagnostics in diabetes mellitus.

Clin Chem Lab Med 44:133-7 (2006)

PMID:12116173 (environmental factor)

Akerblom HK, Vaarala O, Hyoty H, Ilonen J, Knip M

Environmental factors in the etiology of type 1 diabetes.

Am J Med Genet 115:18-29 (2002)

PMID:17203405 (environmental factor)

Peng H, Hagopian W

Environmental factors in the development of Type 1 diabetes.

Rev Endocr Metab Disord 7:149-62 (2006)