The Journal of clinical endocrinology and metabolism · 2025
Genetic Variants Associated With the Biochemical Response to Vitamin D3 in the Multi-Ethnic Study of Atherosclerosis.
СтатьяРандомизированное исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Best Cora M, Li Xiaohui, Rotter Jerome I, Prince David K, Hsu Simon, Hoofnagle Andrew N, Siscovick David, Taylor Kent D, Williams Kayleen, Michos Erin D, Psaty Bruce M, Shea Steven, Rice Kenneth M, Watson Karol E, Allen Norrina B, Tracy Russell P, Robinson-Cohen Cassianne, de Boer Ian H, Kestenbaum Bryan R
Аннотация
CONTEXT: The response to treatment with vitamin D varies between patients.
OBJECTIVE: To identify genetic variants associated with the biochemical response to vitamin D3 supplementation.
DESIGN: Randomized placebo-controlled trial conducted between 2017 and 2019.
SETTING: The trial was nested in an ongoing community-based cohort study, the Multi-Ethnic Study of Atherosclerosis.
INTERVENTION: 2000 International Units of vitamin D3 or placebo daily for 16 weeks.
PARTICIPANTS: The analytic sample included 427 participants assigned to vitamin D3 (mean age, 73 years; 54% females) and was 36% White, 33% Black, 18% Hispanic, and 14% Chinese.
MAIN OUTCOME MEASURES: The biochemical response to vitamin D3 included changes in serum concentrations of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], PTH, and 25-hydroxyvitamin D3 [25(OH)D3].
RESULTS: In genome-wide analyses, single nucleotide polymorphisms in 8 regions of the genome had significant association (P < 5E-08) with 1 of the traits (2 with change in 1,25(OH)2D3, 1 with change in PTH, and 5 with change in 25(OH)D3). rs16867276 within an intergenic region on 2q31 was associated with change in serum 1,25(OH)2D3 (+8.37 pg/mL difference per effect allele; P = 4.93E-08) and was the only locus that achieved genome-wide significance in transethnic meta-analysis. rs114044709 adjacent to FAM20A, which encodes a protein required for biomineralization, was associated with change in PTH among Black participants (+20.32 pg/mL difference per effect allele; P = 1.34E-08). In candidate analyses, single nucleotide polymorphisms within SULT2A1 and CYP24A1 had significant association (P < .05÷36 = .0014) with the changes in 1,25(OH)2D3 and PTH, respectively.
CONCLUSION: Our results reveal potential new pathways of vitamin D regulation that require replication in other vitamin D trials.
OBJECTIVE: To identify genetic variants associated with the biochemical response to vitamin D3 supplementation.
DESIGN: Randomized placebo-controlled trial conducted between 2017 and 2019.
SETTING: The trial was nested in an ongoing community-based cohort study, the Multi-Ethnic Study of Atherosclerosis.
INTERVENTION: 2000 International Units of vitamin D3 or placebo daily for 16 weeks.
PARTICIPANTS: The analytic sample included 427 participants assigned to vitamin D3 (mean age, 73 years; 54% females) and was 36% White, 33% Black, 18% Hispanic, and 14% Chinese.
MAIN OUTCOME MEASURES: The biochemical response to vitamin D3 included changes in serum concentrations of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], PTH, and 25-hydroxyvitamin D3 [25(OH)D3].
RESULTS: In genome-wide analyses, single nucleotide polymorphisms in 8 regions of the genome had significant association (P < 5E-08) with 1 of the traits (2 with change in 1,25(OH)2D3, 1 with change in PTH, and 5 with change in 25(OH)D3). rs16867276 within an intergenic region on 2q31 was associated with change in serum 1,25(OH)2D3 (+8.37 pg/mL difference per effect allele; P = 4.93E-08) and was the only locus that achieved genome-wide significance in transethnic meta-analysis. rs114044709 adjacent to FAM20A, which encodes a protein required for biomineralization, was associated with change in PTH among Black participants (+20.32 pg/mL difference per effect allele; P = 1.34E-08). In candidate analyses, single nucleotide polymorphisms within SULT2A1 and CYP24A1 had significant association (P < .05÷36 = .0014) with the changes in 1,25(OH)2D3 and PTH, respectively.
CONCLUSION: Our results reveal potential new pathways of vitamin D regulation that require replication in other vitamin D trials.