Genetic similarities between latent autoimmune diabetes in adults, type 1 diabetes, and type 2 diabetes.
OBJECTIVE
Latent autoimmune diabetes in adults (LADA) is often considered a slowly progressing subtype of type 1 diabetes, although the clinical picture more resembles type 2 diabetes. One way to improve classification is to study whether LADA shares genetic features with type 1 and/or type 2 diabetes.


METHODS
To accomplish this, we studied whether LADA shares variation in the HLA locus or INS VNTR and PTPN22 genes with type 1 diabetes or the TCF7L2 gene with type 2 diabetes in 361 LADA, 718 type 1 diabetic, and 1,676 type 2 diabetic patients, as well as 1,704 healthy control subjects from Sweden and Finland.


RESULTS
LADA subjects showed, compared with type 2 diabetic patients, increased frequency of risk for the HLA-DQB1 *0201/*0302 genotype (27 vs. 6.9%; P < 1 x 10(-6)), with similar frequency as with type 1 diabetes (36%). In addition, LADA subjects showed higher frequencies of protective HLA-DQB1 *0602(3)/X than type 1 diabetic patients (8.1 vs. 3.2%, P = 0.003). The AA genotype of rs689, referring to the class I allele in the INS VNTR, as well as the CT/TT genotypes of rs2476601 in the PTPN22 gene, were increased both in type 1 diabetic (P = 3 x 10(-14) and P = 1 x 10(-10), respectively) and LADA (P = 0.001 and P = 0.002) subjects compared with control subjects. Notably, the frequency of the type 2 diabetes-associated CT/TT genotypes of rs7903146 in the TCF7L2 were increased in LADA subjects (52.8%; P = 0.03), to the same extent as in type 2 diabetic subjects (54.1%, P = 3 x 10(-7)), compared with control subjects (44.8%) and type 1 diabetic subjects (43.3%).


CONCLUSIONS
LADA shares genetic features with both type 1 (HLA, INS VNTR, and PTPN22) and type 2 (TCF7L2) diabetes, which justifies considering LADA as an admixture of the two major types of diabetes.
Cervin
Camilla
C
Department of Clinical Sciences-Diabetes & Endocrinology, Clinical Research Center, Malmö University Hospital, Lund University, S-205 02 Malmö, Sweden.
Lyssenko
Valeriya
V
Bakhtadze
Ekaterine
E
Lindholm
Eero
E
Nilsson
Peter
P
Tuomi
Tiinamaija
T
Cilio
Corrado M
CM
Groop
Leif
L
D000328:Adult; D017668:Age of Onset; D000368:Aged; D015992:Body Mass Index; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000276:immunology; D005260:Female; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000235:genetics; D012016:Reference Values
D006680:HLA Antigens; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1