VDR polymorphisms influence the immune response in type 1 diabetic children from Santiago, Chile

Abstract 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 D3 , auto-antibodies, and INFγ/TGFβ1 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 GAD65 auto-antibodies, 25-hydroxyvitamin D3 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 D3 levels showed no differences between type 1 diabetic and healthy children. In cases, 25-hydroxyvitamin D3 levels were not associated with a special auto-antibodies profile according to the presence or absence of GAD65+ 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 TGFβ1 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 GAD65 , IA-2 and TGFβ1 were observed among diabetic children. Conclusion 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 GAD65 , IA-2 and TGFβ1.