Genetic Components of 25-Hydroxyvitamin D Increase in Three Randomized Controlled Trials

Area of Science:

• Nutrigenetics
• Endocrinology
• Human Genetics

Background:

• Serum 25-hydroxyvitamin D (25[OH]D) levels are influenced by intake, production, and genetics.
• Genome-wide association studies identify single nucleotide polymorphisms (SNPs) in vitamin D metabolism genes impacting 25[OH]D levels.
• Mechanisms linking specific SNPs to serum 25[OH]D modulation remain largely unknown.

Purpose of the Study:

• To investigate the impact of ten selected vitamin D metabolism SNPs on the increase in 25-hydroxyvitamin D (∆25[OH]D) following supplementation.
• To analyze genetic effects on vitamin D status improvement in individuals with suboptimal levels.

Main Methods:

• Genotyping of ten vitamin D metabolism SNPs in 411 participants with baseline 25[OH]D < 75 nmol/l.
• Participants received 20,000 IU cholecalciferol weekly for 8 or 12 weeks.
• Analysis of ∆25[OH]D in relation to VDR rs10783219 polymorphism.

Main Results:

• The minor A-allele of the vitamin D receptor (VDR) rs10783219 polymorphism was associated with significantly lower ∆25[OH]D (p=0.022).
• This association was observed in the overall population but lacked consistency across individual cohorts.
• No significant association was found for the other nine SNPs investigated.

Conclusions:

• The VDR rs10783219 polymorphism may act as a genetic modulator influencing the increase in serum 25-hydroxyvitamin D concentrations after supplementation.
• Further large-scale randomized controlled trials are warranted to confirm the clinical significance of this VDR polymorphism in vitamin D supplementation response.