Abstract
Vitamin D has been considered a strong contributing factor to type 1 diabetes mellitus (T1DM). Many studies have investigated polymorphisms in the VDR gene in association with T1DM in different populations, but there are still conflicting findings. This study aimed to evaluate the association of four variants in the VDR gene (rs7975232, rs1544410, rs731236, and rs2228570) with T1DM risk and vitamin D levels within a population from North Region, Brazil, as well as the influence of genomic ancestry on T1DM. A total of 65 T1DM patients and 83 non-T1DM patients were enrolled in this study. VDR gene polymorphisms were assessed using Sanger sequencing analysis. Genomic ancestry was analyzed using a set of 61 ancestry-informative markers. T1DM patients showed higher European genomic contribution and lower Native American genomic contribution when compared to non-T1DM patients. T1DM patients with AA genotype in rs1544410 or CC genotype in rs731236 had significantly lower 25(OH)D levels compared to the other two genotypes (p = 0.013 and p = 0.02, respectively), while T1DM with TT genotype in rs2228570 had higher 25(OH)D levels compared to CC + TC in the same polymorphism (p = 0.011). Our findings suggest that the association between 25(OH)D and T1DM may be modified by VDR variants, possibly influencing the development of this autoimmune disease.
Highlights
Type 1 diabetes mellitus (T1DM) is an autoimmune disease caused by complex interactions between immunological, genetic, epigenetic, and environmental factors, leading to the destruction of pancreatic β-cells and subsequent insulin deficiency [1]
Significant differences were detected in the sex, age, weight, and body mass index (BMI)
Given the possible role that vitamin D plays in autoimmune diseases, its levels have been investigated in type 1 diabetes mellitus (T1DM) patients [31]
Summary
Type 1 diabetes mellitus (T1DM) is an autoimmune disease caused by complex interactions between immunological, genetic, epigenetic, and environmental factors, leading to the destruction of pancreatic β-cells and subsequent insulin deficiency [1]. T1DM affects any age group, the onset occurs most frequently in children and adolescents. Vitamin D has been considered an important factor to T1DM [3], given the high prevalence of vitamin D deficiency in T1DM patients compared to nondiabetic subjects and its impact on glycemic control [4]. Vitamin D has many immunomodulatory effects, including increased infiltration of regulatory T cells, inhibition of Th1 infiltration, and decreased expression of inflammatory chemokines and cytokines (e.g., IL-1β, IP-10, IL-15). Together, these effects lead to reduced severity of insulitis and preserved β-cell functionality, inhibiting the development of T1DM [5–7].
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