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- Sallinen, Riitta J., et al.
(författare)
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Genetic Risk Score for Serum 25-Hydroxyvitamin D Concentration Helps to Guide Personalized Vitamin D Supplementation in Healthy Finnish Adults
- 2021
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Ingår i: Journal of Nutrition. - : Elsevier BV. - 0022-3166 .- 1541-6100. ; 151:2, s. 281-292
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genetic factors modify serum 25-hydroxyvitamin D [25(OH)D] concentration and can affect the optimal intake of vitamin D.Objectives: We aimed to personalize vitamin D supplementation by applying knowledge of genetic factors affecting serum 25(OH)D concentration.Methods: We performed a genome-wide association study of serum 25(OH)D concentration in the Finnish Health 2011 cohort (n = 3339) using linear regression and applied the results to develop a population-matched genetic risk score (GRS) for serum 25(OH)D. This GRS was used to tailor vitamin D supplementation for 96 participants of a longitudinal Digital Health Revolution (DHR) Study. The GRS, serum 25(OH)D concentrations, and personalized supplementation and dietary advice were electronically returned to participants. Serum 25(OH)D concentrations were assessed using immunoassays and vitamin D intake using FFQs. In data analyses, cross-sectional and repeated-measures statistical tests and models were applied as described in detail elsewhere.Results: GC vitamin D-binding protein and cytochrome P450 family 2 subfamily R polypeptide 1 genes showed genome-wide significant associations with serum 25(OH)D concentration. One single nucleotide polymorphism from each locus (rs4588 and rs10741657) was used to develop the GRS. After returning data to the DHR Study participants, daily vitamin D supplement users increased from 32.6% to 60.2% (P = 6.5 x 10(-6)) and serum 25(OH)D concentration from 64.4 +/- 20.9 nmol/L to 68.5 +/- 19.2 nmol/L (P = 0.006) between August and November. Notably, the difference in serum 25(OH)D concentrations between participants with no risk alleles and those with 3 or 4 risk alleles decreased from 20.7 nmol/L to 8.0 nmol/L (P = 0.0063).Conclusions: We developed and applied a population-matched GRS to identify individuals genetically predisposed to low serum 25(OH)D concentration. We show how the electronic return of individual genetic risk, serum 25(OH)D concentrations, and factors affecting vitamin D status can be used to tailor vitamin D supplementation. This model could be applied to other populations and countries.
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| 2. |
- Virtanen, Jyrki K., et al.
(författare)
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Vitamin D supplementation and prevention of cardiovascular disease and cancer in the Finnish Vitamin D Trial : a randomized controlled trial
- 2022
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Ingår i: American Journal of Clinical Nutrition. - : Oxford University Press. - 0002-9165 .- 1938-3207. ; 115:5, s. 1300-1310
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Vitamin D insufficiency is associated with risk of cardiovascular diseases (CVD) and cancer in observational studies, but evidence for benefits with vitamin D supplementation is limited.OBJECTIVES: To investigate the effects of vitamin D3 supplementation on CVD and cancer incidence.DESIGN: The study was a 5-year randomized placebo-controlled trial among 2495 male participants ≥ 60 years and post-menopausal female participants ≥ 65 years from a general Finnish population who were free of prior CVD or cancer. The study had three arms: placebo, 1600 IU/day or 3200 IU/day vitamin D3. Follow-up was by annual study questionnaires and national registry data. A representative sub-cohort of 551 participants had more detailed in-person investigations. The primary endpoints were incident major CVD and invasive cancer. Secondary endpoints included the individual components of the primary CVD endpoint (myocardial infarction, stroke, and CVD mortality), site-specific cancers and cancer death.RESULTS: During the follow-up, there were 41 (4.9%), 42 (5.0%) and 36 (4.3%) major CVD events in the placebo, 1600 IU/d (vs. placebo: hazard ratio (HR), 0.97;95% CI, 0.63,1.49; P = 0.89), and 3200 IU/d (HR, 0.84;95% CI, 0.54,1.31; P = 0.44) arms, respectively. Invasive cancer was diagnosed in 41 (4.9%), 48 (5.8%) and 40 (4.8%) participants in the placebo, 1600 IU/d (HR, 1.14;95% CI, 0.75,1.72; P = 0.55), and 3200 IU/d (HR, 0.95;95% CI, 0.61,1.47; P = 0.81) arms, respectively. There were no significant differences in the secondary endpoints or total mortality. In the sub-cohort, the mean (standard deviation) baseline serum 25-hydroxyvitamin D concentration was 75 (18) nmol/L. After 12 months, the concentrations were 73 (18) nmol/L, 100 (21) nmol/L and 120 (22) nmol/L in the placebo, 1600 IU/d and 3200 IU/d arms, respectively.CONCLUSIONS: Vitamin D3 supplementation did not lower the incidence of major CVD events or invasive cancer among older adults, possibly due to sufficient vitamin D status in most participants at baseline. Clinical Trial Registry number: ClinicalTrials.gov: NCT01463813, https://clinicaltrials.gov/ct2/show/NCT01463813.
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