Differences in the genetic background of latent autoimmune diabetes in adults (LADA) and type 1 diabetes mellitus.
OBJECTIVE
According to the recent classification of diabetes mellitus the Latent Autoimmune Diabetes in Adults (LADA) belongs to the group of type 1 autoimmune diabetes, as a slowly progressive form. Our aim was to determine (i) the prevalence of HLA-DRB1 and DQB1 genotypes, and (ii) to determine the tumor necrosis factor (TNF) alpha promoter polymorphism at position -308 (the G-->A substitution, designated the TNF2 allele) in patients with type 1 diabetes and with LADA compared with the healthy population.


METHODS
The major histocompatibility complex (MHC) II genotypes and the TNF alpha promoter polymorphism were determined by PCR method. We examined 69 type 1 diabetic and 42 LADA patients. As control samples of 336 cadaver kidney donors and 138 volunteers were used.


RESULTS
Both type 1 diabetes mellitus and LADA were positively associated with the DRB1*04-DQB1*0302 (DR4/DQ8) haplotype (P=0.00001, and P=0.0005, respectively), and negatively associated with the DRB1*11-DQB1*0301 (DR11/DQ7) haplotype (P=0.00006, and P=0.007, respectively) compared with control population. There were differences between the two disease entities in the frequency of the DRB1*03-DQB1*02 (DR3/DQ2) haplotype (P=0.00008 vs. P=0.177) compared with control group. The presence of the TNF2 allele was significantly lower in LADA than type I diabetes (P=0.022) or control group (P=0.017).


CONCLUSIONS
Our findings indicate that there are marked differences in the genetic background of type 1 diabetes and LADA. The low presence of TNF2 allele (known to be associated with high amount of TNF alpha production) in LADA could be one of the factors responsible for the relatively slow progression.
Vatay
Agnes
A
3rd Department of Internal Medicine, Semmelweis University, Kútvölgyi út 4, 1125 Budapest, Hungary.
Rajczy
Katalin
K
Pozsonyi
Eva
E
Hosszúfalusi
Nóra
N
Prohászka
Zoltán
Z
Füst
George
G
Karádi
István
I
Szalai
Csaba
C
Grósz
Andrea
A
Bártfai
Zoltán
Z
Pánczél
Pál
P
D000328:Adult; D001327:Autoimmune Diseases / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D005802:Genes, MHC Class II / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D014409:Tumor Necrosis Factor-alpha