Latent autoimmune diabetes in adults differs genetically from classical type 1 diabetes diagnosed after the age of 35 years.
OBJECTIVE
We studied differences between patients with latent autoimmune diabetes in adults (LADA), type 2 diabetes, and classical type 1 diabetes diagnosed after age 35 years.


METHODS
Polymorphisms in HLA-DQB1, INS, PTPN22, and CTLA4 were genotyped in patients with LADA (n = 213), type 1 diabetes diagnosed at >35 years of age (T1D(>35y); n = 257) or <20 years of age (T1D(<20y); n = 158), and type 2 diabetes.


RESULTS
Although patients with LADA had an increased frequency of HLA-DQB1 and PTPN22 risk genotypes and alleles compared with type 2 diabetic subjects, the frequency was significantly lower compared with T1D(>35y) patients. Genotype frequencies, measures of insulin secretion, and metabolic traits within LADA differed according to GAD antibody (GADA) quartiles, but even the highest quartile differed from type 1 diabetes. Having two or more risk genotypes was associated with lower C-peptide concentrations in LADA.


CONCLUSIONS
LADA patients differed genetically and phenotypically from both T1D(>35y) and type 2 diabetic patients in a manner dependent on GADA levels.
Andersen
Mette K
MK
Research Program for Molecular Medicine, Helsinki University, Helsinki, Finland.
Lundgren
Virve
V
Turunen
Joni A
JA
Forsblom
Carol
C
Isomaa
Bo
B
Groop
Per-Henrik
PH
Groop
Leif
L
Tuomi
Tiinamaija
T
D000328:Adult; D000483:Alleles; D015703:Antigens, CD / Q000235:genetics; D060908:CTLA-4 Antigen; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D007328:Insulin; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22
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