Vitamin D deficiency and VDR gene polymorphism FokI (rs2228570) are associated with diabetes mellitus in adults: COVID-Inconfidentes Study

Background: Diabetes mellitus is a chronic and multifactorial condition, including environmental risk factors such as lifestyle habits and genetic conditions. Objective: We aimed to evaluate the association of VDR gene polymorphism (rs2228570) FokI and vitamin D levels with diabetes in adults. Methods: : Cross-sectional population-based study in adults, conducted from October to December 2020 in two Brazilian cities. The outcome variable was diabetes, defined as glycated hemoglobin ≥ 6.5% or self-report medical diagnosis or use of oral hypoglycemic drugs. Vitamin D (25-hydroxyvitamin D) was measured by indirect electrochemiluminescence, and classified as deficiency when 25(OH)D < 20 ng/mL. All participants were genotyped for VDR FokI polymorphism by qPCR and classified as homozygous mutant (ff), heterozygous (Ff), or homozygous wild (FF). The association between the FokI polymorphism, vitamin D levels, and diabetes were estimated using multivariate logistic analysis. A combined analysis between the FokI polymorphism and vitamin D levels with diabetes was also examined. A directed acyclic graph (DAG) was used to select minimal and sufficient adjustment for confounding variables by the backdoor criterion. Results: : The prevalence of DM was 9.4% and vitamin D deficiency (VDD) was 19.9%. The genotype distribution of FokI polymorphism was 9.9% FF, 44.8% Ff, and 45.3% ff. It was possible to verify a positive association between vitamin D deficiency and DM (OR= 2.19; 95% CI: 1.06-4.50). Individuals with the altered allele (ff) had a 1.78 higher prevalence of DM (OR: 1.78; 95% CI; 1.10-2.87). Combined analyses, individuals with vitamin D deficiency and one or two copies of the altered FokI allele had a higher prevalence of DM (Ff + ff: OR: 1.67; 95% CI; 1.07-2.61; ff: OR: 3.60; 95% CI; 1.40-9.25). Conclusion: Our data suggest that vitamin D deficiency and FokI polymorphism are associated with DM.