title: Genetic Ancestry, Skin Reflectance and Pigmentation Genotypes in Association with Serum Vitamin D Metabolite Balance.
abstract: 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 (SLC45A2andSLC24A5).
  
  
  
  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)D2and 24,25(OH)2D3) were determined by high performance liquid chromatography (HPLC) tandem mass spectrometry. Percent 24,25(OH)2D3was 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 withSLC24A5111Thrhomozygotes, individuals with theSLC24A5111Thr/Alaand 111Ala/Alagenotypes 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.
  
  
  
  TheSLC24A5111Alaallele was associated with lower serum vitamin 25(OH)D3and lower percent 24,25(OH)2D3, independently from melanin index and West African genetic ancestry.
authors.affiliation: Penn State Hershey College of Medicine, and Penn State Hershey Cancer Institute, The Pennsylvania State University, Hershey, Pennsylvania, U.S.A.
authors.forename: Robin Taylor
authors.initials: RT
authors.lastname: Wilson
authors.forename: Alanna N
authors.initials: AN
authors.lastname: Roff
authors.forename: P Jenny
authors.initials: PJ
authors.lastname: Dai
authors.forename: Tracey
authors.initials: T
authors.lastname: Fortugno
authors.forename: Jonathan
authors.initials: J
authors.lastname: Douds
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Gary L
authors.initials: GL
authors.lastname: Grove
authors.forename: Sheila Ongeri
authors.initials: SO
authors.lastname: Nikiforova
authors.forename: Jill
authors.initials: J
authors.lastname: Barnholtz-Sloan
authors.forename: Tony
authors.initials: T
authors.lastname: Frudakis
authors.forename: Vernon M
authors.initials: VM
authors.lastname: Chinchilli
authors.forename: Terryl J
authors.initials: TJ
authors.lastname: Hartman
authors.forename: Laurence M
authors.initials: LM
authors.lastname: Demers
authors.forename: Mark D
authors.initials: MD
authors.lastname: Shriver
authors.forename: Victor A
authors.initials: VA
authors.lastname: Canfield
authors.forename: Keith C
authors.initials: KC
authors.lastname: Cheng
keywords: 24,25-Dihydroxyvitamin D 3; 25-hydroxyvitamin D; African Continental Ancestry Group; European Continental Ancestry Group; SLC24A5