Genetic Ancestry, Skin Reflectance and Pigmentation Genotypes in Association with Serum Vitamin D Metabolite Balance

Lower serum vitamin D (25(OH)D) among individuals with African ancestry is attributed primarily to skin pigmentation. However, the influence of genetic polymorphisms controlling for skin melanin content has not been investigated. Therefore, we investigated differences in non-summer serum vitamin D metabolites according to self-reported race, genetic ancestry, skin reflectance and key pigmentation genes (SLC45A2 and SLC24A5).

Healthy individuals reporting at least half African American or half European American heritage were frequency matched to one another on age (+/- 2 years) and sex. 176 autosomal ancestry informative markers were used to estimate genetic ancestry. Melanin index was measured by reflectance spectrometry. Serum vitamin D metabolites (25(OH)D₃, 25(OH)D ₂ and 24,25(OH)₂D₃) were determined by high performance liquid chromatography (HPLC) tandem mass spectrometry. Percent 24,25(OH)₂D₃ was calculated as a percent of the parent metabolite (25(OH)D₃). Stepwise and backward selection regression models were used to identify leading covariates.

Fifty African Americans and 50 European Americans participated in the study. Compared with SLC24A5 111^Thr homozygotes, individuals with the SLC24A5 111^Thr/Ala and 111^Ala/Ala genotypes had respectively lower levels of 25(OH)D₃ (23.0 and 23.8 nmol/L lower, p-dominant=0.007), and percent 24,25(OH)₂D₃ (4.1 and 5.2 percent lower, p-dominant=0.003), controlling for tanning bed use, vitamin D/fish oil supplement intake, race/ethnicity, and genetic ancestry. Results were similar with melanin index adjustment, and were not confounded by glucocorticoid, oral contraceptive, or statin use.

The SLC24A5 111^Ala allele was associated with lower serum vitamin 25(OH)D₃ and lower percent 24,25(OH)₂D₃, independently from melanin index and West African genetic ancestry.