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Multi-ethnic analysis shows genetic risk and environmental predictors interact to influence 25(OH)D concentration and optimal vitamin D intake.

ABSTRACT: 25-Hydroxyvitamin D (25(OH)D) concentration is a complex trait with genetic and environmental predictors that may determine how much vitamin D exposure is required to reach optimal concentration. Interactions between continuous measures of a polygenic score (PGS) and vitamin D intake (PGS*intake) or available ultraviolet (UV) radiation (PGS*UV) were evaluated in individuals of African (n?=?1,099) or European (n?=?8,569) ancestries. Interaction terms and joint effects (main and interaction terms) were tested using one-degree of freedom (1-DF) and 2-DF models, respectively. Models controlled for age, sex, body mass index, cohort, and dietary intake/available UV. In addition, in participants achieving Institute of Medicine (IOM) vitamin D intake recommendations, 25(OH)D was evaluated by level PGS. The 2-DF PGS*intake, 1-DF PGS*UV, and 2-DF PGS*UV results were statistically significant in participants of European ancestry (p?=?3.3?×?10^-18 , p?=??2.1?×?10^-2 , and p?=??2.4?×?10^-19 , respectively), but not in those of African ancestry. In European-ancestry participants reaching IOM vitamin D intake guidelines, the percent of participants achieving adequate 25(OH)D ( >20?ng/ml) increased as genetic risk decreased (72% vs. 89% in highest vs. lowest risk; p?=?.018). Available UV radiation and vitamin D intake interact with genetics to influence 25(OH)D. Individuals with higher genetic risk may require more vitamin D exposure to maintain optimal 25(OH)D concentrations.

SUBMITTER: Hatchell KE

PROVIDER: S-EPMC7028464 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Multi-ethnic analysis shows genetic risk and environmental predictors interact to influence 25(OH)D concentration and optimal vitamin D intake.

Hatchell Kathryn E KE Lu Qiongshi Q Mares Julie A JA Michos Erin D ED Wood Alexis C AC Engelman Corinne D CD

Genetic epidemiology 20191212 2

25-Hydroxyvitamin D (25(OH)D) concentration is a complex trait with genetic and environmental predictors that may determine how much vitamin D exposure is required to reach optimal concentration. Interactions between continuous measures of a polygenic score (PGS) and vitamin D intake (PGS*intake) or available ultraviolet (UV) radiation (PGS*UV) were evaluated in individuals of African (n = 1,099) or European (n = 8,569) ancestries. Interaction terms and joint effects (main and interaction terms) ...[more]

PMID: 31830327

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Project description:ContextThere is uncertainty over the equivalence of vitamins D2 and D3 to maintain plasma 25-hydroxyvitamin D (25(OH)D).ObjectiveThe objective of the study was to compare the plasma half-lives of 25(OH)D2 and 25(OH)D3 in two distinct populations with different dietary calcium intake and 25(OH)D status.ParticipantsHealthy men (aged 24 and 39 y), resident in The Gambia (n = 18) or the United Kingdom (n = 18) participated in the study.InterventionsThe intervention included an oral tracer dose of deuterated-25(OH)D2 and deuterated-25(OH)D3 (both 40 nmol). Blood samples were collected over 33 days.Main outcome measures25(OH)D2 and 25(OH)D3 plasma half-lives, concentrations of 25(OH)D, and vitamin D binding protein (DBP) and DBP genotypes were measured.Results25(OH)D2 half-life [mean (SD)] [13.9 (2.6) d] was shorter than 25(OH)D3 half-life [15.1 (3.1) d; P = .001] for countries combined, and in Gambians [12.8 (2.3) d vs 14.7 (3.5) d; P < .001], but not in the United Kingdom [15.1 (2.4) d vs 15.6 (2.5) d; P = .3]. 25(OH)D concentration was 69 (13) and 29 (11) nmol/L (P < .0001), and the DBP concentration was 259 (33) and 269 (23) mg/L (P = .4) in The Gambia and United Kingdom, respectively. Half-lives were positively associated with plasma DBP concentration for countries combined [25(OH)D2 half-life: regression coefficient (SE) 0.03 (0.01) d per 1 mg/L DBP, P = .03; 25(OH)D3 half-life: 0.04 (0.02) d, P = .02] and in Gambians [25(OH)D2 half-life: 0.04 (0.01) d; P = .02; 25(OH)D3 half-life: 0.06 (0.02) d, P = .01] but not in UK participants. The DBP concentration × country interactions were not significant. DBP Gc1f/1f homozygotes had shorter 25(OH)D2 half-lives compared with other combined genotypes (P = .007) after correction for country.Conclusions25(OH)D2 half-life was shorter than 25(OH)D3 half-life, and half-lives were affected by DBP concentration and genotype. The stable isotope 25(OH)D half-life measurements provide a novel tool to investigate vitamin D metabolism and vitamin D expenditure and aid in the assessment of vitamin D requirements.

Dataset Information

Multi-ethnic analysis shows genetic risk and environmental predictors interact to influence 25(OH)D concentration and optimal vitamin D intake.

Publications

Multi-ethnic analysis shows genetic risk and environmental predictors interact to influence 25(OH)D concentration and optimal vitamin D intake.

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