Diabetes mellitus in adults: association of HLA DRB1 and DQB1 diabetes risk alleles with GADab presence and C-peptide secretion.
In our study, we investigated the relationship of HLA class II alleles to antibody production against glutamic acid decarboxylase (GADab) and to C-peptide secretion (CP) in diabetic patients. A group of 334 patients (190 women) diagnosed after 35 years of age and 99 control subjects were studied. Patients were divided into four groups according to concentrations of CP and GADab, respectively (CP high/low, GADab positive/negative). HLA DQB1 and DRB1 alleles were genotyped by SSP-PCR. The significance of DQB1 and DRB1 risk alleles was evaluated by examination of their odds ratios computed by testing 2x2 tables considering Bonferonis' corrected P<0.05 as significant. We found strong association between the HLA DRB1*03 risk allele and presence of GADab, and close relationship of the HLA DRB1*04 and HLA DQB1*0302 risk alleles with decreased CP level. Taken together we conclude that the DRB1*04 and DQB1*0302 alleles are associated with progressive decrease of CP level, while DRB1*03 is a significant genetic marker of autoantibody (GADab) development.
Novota
Peter
P
Department of Cell and Molecular Biology, The 3rd Faculty of Medicine, Charles University at Prague, Czech Republic. peter.novota@medicon.cz
Cerna
Marie
M
Kolostova
Katarina
K
Cejkova
Pavlina
P
Zdarsky
Emanuel
E
Novakova
Dana
D
Kucera
Petr
P
Novak
Jan
J
Andel
Michal
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000906:Antibodies / Q000276:immunology; D002096:C-Peptide / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000201:enzymology / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005968:Glutamate Decarboxylase / Q000276:immunology / Q000378:metabolism*; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged
D000906:Antibodies; D002096:C-Peptide; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C057615:HLA-DQbeta antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D005968:Glutamate Decarboxylase