Genetic control of serum 25(OH)D levels and its association with ethnicity

Background: Identified DNA variants associated with serum 25-hydroxyvitamin vitamin D (25[OH]D) concentration may provide mechanistic insights into the vitamin D metabolic pathway in individuals. Our aim was to further characterise participants and their serum 25(OH)D concentration at baseline using candidate single nucleotide polymorphism (SNP) genotyping.

Methods: 5110 participants, aged 50-84 years, were recruited from the community. Blood samples were collected at baseline to measure serum 25(OH)D by liquid chromatography mass spectrometry and the participants were genotyped for four markers close to or within genes in the vitamin D metabolic pathway known to be associated with differences in 25(OH)D. The markers and their associated genes were rs12785878 (DHCR7), rs10741657 (CYP2R1), rs4588 (DBP) and rs2228570 (VDR).

Results: All four markers had significantly different genotype distributions and minor allele frequencies between the four self-determined ethnicities (European/Other, Māori, Pacific, and South Asian). For example, the frequency in each ethnic group of the G allele for the marker rs12785878 was 0.26, 0.71, 0.89, and 0.78 respectively. Using multivariable regression in the full cohort, three out of four markers were significantly associated with baseline concentrations of 25(OH)D (mean differences: 2.9-10.9 nmol/L). Collectively, the four markers explained 8.4% of the variation in 25(OH)D concentrations.

Conclusion: Significant ethnic variations exist in the distribution of alleles associated with serum 25(OH)D concentration, particularly rs12785878, in a multi-ethnic community sample from New Zealand.