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

Garcia D.; Ángel B.; Carrasco, E; Albala, C; Santos, JL; Perez-Bravo, F

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 D 3, 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 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 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 GAD 65, 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 GAD 65, IA-2 and TGFβ1. © 2006 Elsevier Ireland Ltd. All rights reserved.

Más información

Título según WOS: VDR polymorphisms influence the immune response in type 1 diabetic children from Santiago, Chile
Título según SCOPUS: VDR polymorphisms influence the immune response in type 1 diabetic children from Santiago, Chile
Título de la Revista: DIABETES RESEARCH AND CLINICAL PRACTICE
Volumen: 77
Número: 1
Editorial: ELSEVIER IRELAND LTD
Fecha de publicación: 2007
Página de inicio: 134
Página final: 140
Idioma: English
URL: http://linkinghub.elsevier.com/retrieve/pii/S016882270600489X
DOI:

10.1016/j.diabres.2006.10.018

Notas: ISI, SCOPUS