Vitamin D Receptor Gene Polymorphism Affects Onset Pattern of Type 1 Diabetes

Abstract

Type 1 diabetes mellitus is recognized as a T-cell-mediated autoimmune disease. Vitamin D compounds are known to suppress T-cell activation by binding to the vitamin D receptor (VDR); and thus, VDR gene polymorphisms may be related to T-cell-mediated autoimmune diseases. We, therefore, investigated a VDR gene polymorphism in type 1 diabetes. We examined the VDR gene Bsm I polymorphism in 203 type 1 diabetic patients and 222 controls, and the association between the VDR gene polymorphism and type 1 diabetes and their onset pattern. We found a significantly higher frequency of B allele in type 1 diabetics overall, compared with controls (P = 0.0010). Moreover, there was a significant difference in B-allele frequency between acute-onset type 1 diabetics and controls (P = 0.0002), whereas this difference was not observed between slow-onset type 1 diabetics and controls. Regardless of the existence of islet-associated autoantibody, we found a significant difference in B-allele frequency between acute-onset type 1 diabetics and controls. In conclusion, we found an association between a VDR gene polymorphism and acute-onset type 1 diabetes. Assessment of this VDR gene polymorphism may contribute to prediction of the onset pattern in individuals with a high risk of type 1 diabetes.

Vitamin D receptor polymorphisms: no association with type 1 diabetes in the Finnish population

“…First, we noticed an SNP at position 76945 in the GenBank contig NT_009526. This SNP is located in the primer region for the BsmI PCR-product used in several previous studies (24,26,29,31). By using a primer three nucleotides shorter than that previously utilised we detected a preferential amplification of a DNA strand with a complementary SNP allele resulting in the misinterpretation of certain BsmI heterozygous genotypes as homozygous ones.…”

“…This might indicate that the above-mentioned SNP was overlooked. A similar bias could have affected the results of other studies reporting BsmI frequencies based on the use of the same primer (24,29,31). Secondly, it is believed that T1D has several different aetiological pathways.…”

Association of vitamin D-related gene polymorphisms with manifestation of vitamin D deficiency in children

“…Moreover, patients harboring the minor BAtS haplotype had a 5.6-fold increased risk of vitamin D deficiency. The minor allele frequency of each VDR polymorphism in the control group was comparable to that in other Japanese controls, indicating no bias in the selection of the control group [27][28][29]. rs10898191 in NADSYN1 is 42 bp away from rs3829251, which has been reported to be associated with reduced 25(OH) ommended for all infants, especially those who are breast-fed [45].…”

“…In particular, minor alleles around the last exon of VDR have been reported to be associated with type 1 diabetes, multiple sclerosis, and prostate cancer in Japanese patients [27][28][29]38]. Vitamin D insufficiency is a risk factor for all these diseases [39].…”

维生素d 在免疫反应和自身免疫性疾病特别是多发性硬化中的作用

“…Besides, in some diseases, a lower 25(OH)D 3 level in serum is correlated with higher disease activities [63] . Additional evidence supporting the role of vitamin D in autoimmunity is the finding of VDR gene polymorphism in patients with autoimmune conditions such as MS [66] , inflammatory bowel diseases [67] , RA [68] , and juvenile diabetes mellitus [69] .…”