<p>Vitamin D receptor rs7975232, rs731236 and rs1544410 single nucleotide polymorphisms, and 25-hydroxyvitamin D levels in Egyptian children with type 1 diabetes mellitus: effect of vitamin D co-therapy</p>

Abstract

Purpose: We aimed to examine the possible association role of vitamin D and vitamin D receptor (VDR) single nucleotide polymorphisms (SNPs) in type 1 diabetes mellitus (T1DM) development, glycemic control and complications among a cohort of Egyptian children. Subjects and methods: A prospective case-control study has been conducted on 50 Egyptian children with T1DM who were comparable with 50 controls. Vitamin D and HbA1c were measured. VDR-SNPs [ Apa I (rs7975232), Taq I (rs731236) and Bsm I (rs1544410)] detection was done by polymerase chain reaction through restriction fragment length polymorphism (PCR-RFLP) technique. Vitamin D supplements were given to the included T1DM children with low vitamin D and reassessments of both HbA1c% and 25(OH)D serum levels were performed in those children three months later. Results: Eighty percent of the included diabetic patients have poor glycemic control. Vitamin D was deficient in 68% and insufficient in 16% of diabetic patients. Significant improvements in both vitamin D and glycemic status among T1DM children, who have low vitamin D and received vitamin D supplementations. There were significantly negative correlations between serum levels of vitamin D with both HbA1c % (r= –0.358, P ˂0.05) and daily insulin dose (r=−0.473, P ˂0.05). Compared with controls, T1DM children presented more commonly with Apa I a allele (OR: 2.87; 95%CI: 1.39–5.91, P ˂0.05) and Bsm I b allele (OR: 4.38; 95%CI: 2.30–8.33, P ˂0.05). Taq I t allele wasn’t significantly differing among patients and controls ( P ˃0.05). Aa+aa and Bb+bb genotypes were significantly higher among T1DM vs the controls (OR: 3.08;, 95%CI: 1.33–7.15, P ˂0.05 and OR: 9.33; 95%CI: 3.61–24.17, P ˂0.05respectively). Conclusion: Apa I and Bsm I were associated with risk of T1DM development among Egyptian children. Low vitamin D status was frequently occurring among T1DM with significant improvement in the glycemic control of such children when adding vitamin D supplements to the standard insulin therapy.

Vitamin D receptor gene polymorphisms and the risk of the type 1 diabetes: a meta-analysis based on 40 case–control studies

“…Furthermore, the results of subgroup analysis according to ethnicity did not show any signi cant association in all genetic models. However, in the subgroup analysis, given that there was only one study in the Australian [57] and American [67] populations, and two studies in the African [56,66] population, the subgroup analysis was not performed in these populations. In line with our ndings, previous meta-analysis by Tizaouia et al…”

“…There were 21 case-control studies with 1973 cases and 1995 controls concerning TaqI polymorphism and T1DM risk. Studies were performed in different population, 8 studies were in Europeans [15,34,35,38,41,42,59,60], 9 studies in Asians [46,48,49,53,[61][62][63][64][65], 2 studies in Africans [56,66] and one study each was in Australia [57] and Americans [67]. Meta-analysis rejected any signi cant association between TaqI SNP and the risk of T1DM susceptibility.…”

“…Moreover, the results of subgroup analysis by ethnicity were not signi cant under ve genotype models. In subgroup analysis, since there was only one study for the Australians [57], Americans [67], and two studies for Africans [56,66], these studies were excluded from the analysis. The results of pooled ORs, heterogeneity tests and publication bias tests in different analysis models are shown in Table 3.…”

“…It was detected that 15 studies with 1938 cases and 4450 controls were performed in European countries [15, 34-38, 40-42, 44, 59, 60] which among these 15 studies, Turpeinen et al [36] conducted an association study in different city of Finland (Turku, Tampere and Oulu) and reported all data separately, including genotype and allele frequency; thus we considered each population as a separate study. Moreover, 14 studies out of 35 eligible studies were carried out in Asian populations [46,48,49,52,53,[61][62][63][64][65][68][69][70][71], 3 studies were in Americans [58,67,72] and three studies were in Africans [54,56,66] Table 3.…”

“…Finally, 24 case-control studies with 2436 cases and 4074 controls were identi ed eligible for quantitative synthesis of the association between ApaI polymorphism and T1DM risk. Overall, 10 studies were conducted in Europe [15,35,36,38,41,42,59,60], 10 studies were in Asia [46, 48-51, 53, 61-64], 2 studies in Africa [56,66] and one study each was in Australia [57] and America [67]. Because of limited number of studies performed in Australia, America and Africa these studies were excluded from subgroup analysis.…”