VDR polymorphisms influence the immune response in type 1 diabetic children from Santiago, Chile.
OBJECTIVE
To evaluate the influence of ApaI, BsmI and TaqI polymorphisms of the VDR gene and HLA-DQB1* alleles in type 1 diabetic children and to assess their possible relationship with circulating levels of 25-hydroxyvitamin D(3), auto-antibodies, and INFgamma/TGFbeta1 cytokines levels in Chilean cases and controls.


METHODS
DNA and serum samples from 216 newly diagnosed type 1 diabetic and 203 unrelated control children were evaluated for IA-2 and GAD(65) auto-antibodies, 25-hydroxyvitamin D(3) levels, HLA-DQB1* alleles, and VDR gene polymorphisms.


RESULTS
The frequency of the b allele and the bb genotype in type 1 diabetic patients was significantly lower compared with the control group (0.635 versus 0.749, p<0.01 and 0.370 versus 0.567, p<0.04). 25-Hydroxyvitamin D(3) levels showed no differences between type 1 diabetic and healthy children. In cases, 25-hydroxyvitamin D(3) levels were not associated with a special auto-antibodies profile according to the presence or absence of GAD(65)(+) or IA-2(+). The haplotype combination BAT was higher in cases (0.062 versus 0.019, p<0.0022) and bAT was more frequent in controls (0.266 versus 0.180, p<0.003). In cases, the aaBbTT genotype showed the most significant increase in TGFbeta1 level across the VDR categories. Finally, when considering the HLA class II risk genotype (DQB1*0302) and the VDR genotypes (AabbTT and aabbTT), higher levels of GAD(65), IA-2 and TGFbeta1 were observed among diabetic children.


CONCLUSIONS
We found an association between a VDR polymorphism (BsmI) and type 1 diabetes. An association was found of AabbTT and aabbTT genotypes and the HLA-DQB1*0302 allele with high levels of GAD(65), IA-2 and TGFbeta1.
García
Diego
D
Genetic Epidemiology Laboratory, Nutrition and Food Technology Institute, University of Chile, Santiago, Chile.
Angel
Bárbara
B
Carrasco
Elena
E
Albala
Cecilia
C
Santos
José Luis
JL
Pérez-Bravo
Francisco
F
D001323:Autoantibodies / Q000032:analysis* / Q000097:blood; D002112:Calcifediol / Q000097:blood; D002648:Child; D002677:Chile; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007527:Isoenzymes / Q000276:immunology; D008297:Male; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000097:blood
D001323:Autoantibodies; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; C096322:ICA512 autoantibody; D007527:Isoenzymes; D018167:Receptors, Calcitriol; D053773:Transforming Growth Factor beta1; D007371:Interferon-gamma; C053864:endodeoxyribonuclease BsmI; D015252:Deoxyribonucleases, Type II Site-Specific; C038485:GGGCCC-specific type II deoxyribonucleases; C027046:TCGA-specific type II deoxyribonucleases; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2; D002112:Calcifediol