Influence of the vitamin D plasma level and vitamin D-related genetic polymorphisms on the immune status of patients with type 1 diabetes: A pilot study

Pharmazentrum Frankfurt/ZAFES.
Clinical & Experimental Immunology (Impact Factor: 3.04). 02/2013; 171(2):171-85. DOI: 10.1111/cei.12013
Source: PubMed


Vitamin D (VD) has been implicated in type 1 diabetes (T1D) by genetic and epidemiological studies. Individuals living in regions with low sunlight exposure have an increased T1D risk and VD supplementation reduced the risk in human individuals and mouse models. One possibility of how VD influences the pathogenesis of T1D is its immunomodulatory effect on dendritic cells (DC), which then preferentially activate regulatory T cells (T(regs) ). In the present pilot study, we collected blood samples from a small cohort of patients with T1D at baseline and months 6 and 12. VD-deficient patients were advised to supplement with 1000 IU/day VD. We found a considerable variation in the VD plasma level at baseline and follow-up. However, with higher VD plasma levels, a lower frequency of interleukin (IL)-4-producing CD8 T cells was observed. We further performed a comprehensive genotyping of 13 VD-related polymorphisms and found an association between VD plasma level and the genotype of the VD binding protein (DBP). The frequency of DC and T cell subsets was variable in patients of all subgroups and in individual patients over time. Nevertheless, we found some significant associations, including the 1,25-dihydroxyvitamin D(3) hydroxylase (CYP27B1) genotype with the frequency of DC subtypes. In summary, our preliminary results indicate only a limited influence of the VD plasma level on the immune balance in patients with T1D. Nevertheless, our pilot study provides a basis for a follow-up study with a larger cohort of patients.

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    • "Genotyping of IL28B was performed as described before [25]. For the determination of CYP2R1- (rs10741657), CYP27B1-(rs10877012) and DBP (rs4588 and rs7041) polymorphisms DNA was amplified with the respective primers, with PCR conditions and enzymes as previously described [26], [27]. The polymorphisms within the DHCR7 reductase-gene (rs12785878/C_32063037_10 and rs7944926/C_12043682_10), DBP (rs2282679/C_26407519_10) and CYP24A1- (rs6013897/C_22958084_10) were analyzed in the laboratory of molecular endocrinology of our department using Taqman assays in an ABI 7300 PCR System under the conditions recommended by the manufacturer (Applied Biosystems, Darmstadt, Germany) as previously described [26]. "
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