Variability in response to vitamin D supplementation according to vitamin D metabolism related gene polymorphisms in healthy adults

Abstract

Objective The aim of this study was to determine the influence of polymorphisms in some key gene actors of the vitamin D (vitD) metabolic pathway on supplementation efficacy. Methods In total, 245 healthy participants were recruited from occupational medicine service in Sahloul University Hospital with vitD deficiency [25(OH)D ≤ 30 ng/ml]. After giving an informed consent, all participants were asked to complete a generalized questionnaire and to follow a detailed personalized supplementation protocol. Genetic study was performed by PCR-RFLP for 15 single nucleotide polymorphisms (SNPs) belonging to DBP, CYP2R1, CYP27B14, CYP24A1 and VDR genes. Statistical study was carried out with SPSS23.0. Results Among the studied SNPs, non-response was significantly associated with variant alleles of rs4588 (OR* = 11.51; p < 0.001), rs10766197 (OR* = 6.92; p = 0.008) and rs12794714 (OR* = 5.09; p = 0.004). These three SNPs contributed in 18.8% in response variability with rs4588 being the most influential (10.3%). There was a significant linear negative correlation between baseline 25(OH)D and post supplementation 25(OH)D concentration ( r = −0.437; p < 0.001) as well as a linear negative association between the increase in 25(OH)D concentration and GRS (GRS: genetic risk score = the sum of risk alleles) ( r = −0.149; p = 0.033). Conclusions DBP-rs4588, CYP2R1-rs10766197 and rs12794714 variants are associated with variations in serum 25(OH)D concentrations and efficacy of response to vitD supplementation in Tunisian adults. Taking into account these variations can help to better adapt vitD intake to ensure a higher response to supplementation.

The impact of genetic variants related to vitamin D and autoimmunity: A systematic review

“…These findings also extend to studies with the adult population. A recent study with healthy adults showed that DBP rs4588 minor allele (TT), CYP2R1 rs10766197 minor allele (AA) and rs12794714 minor allele (AA) were associated with lower response to vit D supplementation [ 174 ].…”

Correlation between maternal and umbilical cord 25-hydroxy-vitamin D levels over a range of values. A prospective observational study from the United Arab Emirates

“…Although the maternal level of 25(OH)D is thought to increase simultaneously and corresponding to oral intake of vitamin D, there is growing evidence for an individual response due to differences in the absorption dependent on our genetics/epigenetics, why it is speculated if some require a higher dose than others to be sufficiently substituted [ 33 , 34 ]. However, results from regions with similar latitudes has shown a significant correlation between UCB and maternal 25(OH)D 3 in un-supplemented women whereas in a predominantly white population from a northern latitude the main predictor for UCB 25(OH)D was delivery in the summer months [ 10 , 35 ].…”

Scientific opinion on the tolerable upper intake level for vitamin D, including the derivation of a conversion factor for calcidiol monohydrate

“…In a Danish study (Nissen et al., 2015 ), common mutations in the CYP2R1 and GC showed the lowest increase in serum 25(OH)D after whole‐body UV‐B radiation or consumption of vitamin D 3 –fortified bread and milk, the effect being comparable for both treatments. Mutations in these two genes were also significantly associated with variations in serum 25(OH)D concentrations and efficacy of response to vitamin D supplementation in Tunisian adults (Ammar et al., 2022 ). In a Chinese study (Yao et al., 2017 ), genetic factors (mutations in the GS , VDR and CYP2R1 genes) showed a larger impact on serum 25(OH)D after supplementation with 50 μg/day vitamin D 3 than non‐genetic factors including baseline value, BMI, and sex.…”