Prediction algorithms using genetic and non genetic factors inducing vitamin D deficiency among healthy adults

Abstract Objective An alarming increase in vitamin D (vitD) deficiency even in sunny regions highlights the need for a better understanding of the mechanisms controlling vitD variability. We aimed to study potential variables involved in vitD deficiency among healthy Tunisian adults in order to establish two prediction algorithms: a composite algorithm (CA) that included genetic and non genetic factors and a simple one (SA) including only environmental non genetic factors. These algorithms could be used to predict vitD status and help identify individuals at high risk of vitD deficiency. Methods We screened six key genes (DBP, CYP2R1, CYP27B14, CYP24A1 and VDR) within the vitD metabolic pathway using 15 single nucleotide polymorphism (SNP) markers in across a cohort of 394 unrelated healthy individuals. After giving an informed consent, all participants were asked to complete a generalized questionnaire. Significant confounding factors that may influence the variability in serum 25(OH)D levels were used as covariates for association analyses. Statistical study was carried out with SPSS26.0. Results VitD deficiency correlated positively with albumin (r = 0.135, p = 0.007) and negatively with serum PTH (r = − 0.303, p < 0.001), age (r = − 0.198, P < 0.001), and BMI (r = − 0.143, p = 0.04). Multivariate logistic regression revealed that season, sun screen use, phototype, age, VDR- rs2228570 and CYP24A1- rs6013897 were significant predictors of hypovitaminosis D. Non genetic factors explained 15.6% of the variance in 25(OH)D concentrations while genetic polymorphisms (VDR- rs2228570 and CYP24A1- rs6013897) explained a lower variance of 12%. When combined together, genetic and non genetic factors contributed up to 27.6% in 25(OH)D concentrations variability. Conclusion 25(OH)D deficiency is highly prevalent among healthy adults in Tunisia. It is related to seasonal fluctuations, increasing age, darker skin tones, excessive sunscreen usage, and genetic polymorphisms in the VDR and CYP24A1 genes. The genetic markers could be used as tools in Mendelian randomization analyses of vitD, and they should well be considered when establishing a supplementation protocol in order to prevent 25(OH)D deficiency in the Tunisian population.