Abstract
Several observational studies have examined vitamin D pathway polymorphisms and their association with type 1 diabetes (T1D) susceptibility, with inconclusive results. We aimed to perform a systematic review and meta-analysis assessing associations between selected variants affecting 25-hydroxyvitamin D [25(OH)D] and T1D risk. We conducted a systematic search of Medline, Embase, Web of Science and OpenGWAS updated in April 2021. The following keywords “vitamin D” and/or “single nucleotide polymorphisms (SNPs)” and “T1D” were selected to identify relevant articles. Seven SNPs (or their proxies) in six genes were analysed: CYP2R1 rs10741657, CYP2R1 (low frequency) rs117913124, DHCR7/NADSYN1 rs12785878, GC rs3755967, CYP24A1 rs17216707, AMDHD1 rs10745742 and SEC23A rs8018720. Seven case-control and three cohort studies were eligible for quantitative synthesis (n = 10). Meta-analysis results suggested no association with T1D (range of pooled ORs for all SNPs: 0.97–1.02; p > 0.01). Heterogeneity was found in DHCR7/NADSYN1 rs12785878 (I2: 64.8%, p = 0.02). Sensitivity analysis showed exclusion of any single study did not alter the overall pooled effect. No association with T1D was observed among a Caucasian subgroup. In conclusion, the evidence from the meta-analysis indicates a null association between selected variants affecting serum 25(OH)D concentrations and T1D.
Highlights
Type 1 diabetes (T1D) is a chronic autoimmune disease, resulting from autoimmune degradation of pancreatic ß-cells leading to the inability to produce and/or use insulin [1]
For rs12785878 G/T (DHCR7/NADSYN1), the odds ratio (OR) ranged from 0.78 to 1.06 (Figure 2), with a pooled OR of 0.99
Ethnicity is believed to have a major role in vitamin D synthesis, subgroup analysis on Caucasian participants provided no evidence for an association between the selected
Summary
T1D patients carry a genetic susceptibility to autoimmune disease development, with first-degree relatives of those affected carrying an increased risk of developing the disease [2,3]. Undiagnosed or untreated T1D can result in hyperglycaemia, increasing the risk of developing microvascular and macrovascular injuries/health complications, such as nephropathy, ischemic heart disease and stroke [4]. Estimates of those with T1D below age 20 had risen to over a million in 2017, with evidence of increasing incidence worldwide [5]. There are no established treatments identified for the prevention of T1D and the search for genetic and environmental triggers remains ongoing.
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