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. 2023 Feb;77(2):189-194.
doi: 10.1038/s41430-022-01218-y. Epub 2022 Sep 27.

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

Mariem Ammar  1   2 , Syrine Heni  3   4 , Mohamed Sahbi Tira  3   4 , Yassine Khalij  3   4 , Haithem Hamdouni  3   4 , Dorra Amor  3   4 , Sonia Ksibi  5 , Asma Omezzine  3   4 , Ali Bouslama  3   4
Affiliations

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

Mariem Ammar et al. Eur J Clin Nutr. 2023 Feb.

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Comparison between vitamin D concentrations at baseline and after supplementation according to GRS category.
A At baseline, no significant association was observed between GRS and 25(OH)D concentrations. However, there was a significant linear negative association between GRS and post supplementation 25(OH)D concentration (r = −0.149; p = 0.033). Participants carrying all six risk alleles experienced a reduced response in 25(OH)D (post supplementation 25(OH)D = 24.02 ± 4 ng/ml) compared to those carrying 0 risk allele (post supplementation 25(OH)D = 37.7 ± 8.8 ng/ml). Δ = 25(OH)D increase; GRS genetic risk score. B Adjusted OR of non-responseto vitD supplementation associated to genetic risk score. Adjusted OR including 95% confidence interval due to GRS variation (Adjusted for: season, baseline 25(OH)D, physical activity and albumin). The horizontal dashed line represents the OR reference value 1.
Fig. 2
Fig. 2. Correlation between 25(OH)D increase and baseline concentration.
Scatter plot showing the linear negative correlation between baseline 25(OH)D (ng/ml) and the increase Δ (ng/ml). Lower baseline 25(OH)D concentrations are associated with higher increase values (r = −0.437; p < 0.01).
See this image and copyright information in PMC

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