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

Background: 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 ( and .

Materials And Methods: 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)D, 25(OH)D and 24,25(OH)D) were determined by high performance liquid chromatography (HPLC) tandem mass spectrometry. Percent 24,25(OH)D was calculated as a percent of the parent metabolite (25(OH)D). Stepwise and backward selection regression models were used to identify leading covariates.

Results: Fifty African Americans and 50 European Americans participated in the study. Compared with 111 homozygotes, individuals with the 111 and 111 genotypes had respectively lower levels of 25(OH)D (23.0 and 23.8 nmol/L lower, p-dominant=0.007), and percent 24,25(OH)D (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.

Conclusions: The 111 allele was associated with lower serum vitamin 25(OH)D and lower percent 24,25(OH)D, independently from melanin index and West African genetic ancestry.