Genetic and environmental determinants of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels in Hispanic and African Americans

Context: Vitamin D deficiency is associated with many adverse health outcomes, yet little is known about the genetic epidemiology of vitamin D or its metabolites. Objective: Our objective was to examine the relationship among three vitamin D-related genes and levels of 25-hydroxyvitamin D [ 25( OH) D] and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] in Hispanics (HAs) and African Americans (AAs). Design and Setting: The cross-sectional Insulin Resistance Atherosclerosis Family Study recruited and examined subjects in: Los Angeles, California ( AAs; 513 individuals from 42 families); San Luis Valley (SLV), Colorado ( HAs; 513 individuals from 30 families); and San Antonio ( SA), Texas ( HAs; 504 individuals from 58 families). Main Outcome Measures: Plasma levels of 25( OH) D and 1,25( OH)(2)D were measured. Results: Levels of 25( OH) D were highest in SLV-HAs [18.3 +/- 7.7 ng/ml ( 45.7 +/- 19.2 nmol/liter)], lower in SA-HAs [14.6 +/- 6.4 ng/ml ( 36.4 +/- 16.0 nmol/liter)], and lowest in AAs [11.0 +/- 5.4 ng/ml (27.5 +/- 13.5 nmol/liter)]. Levels of 1,25( OH)(2)D were similar in AAs [43.5 +/- 13.9 pg/ml (113.1 +/- 36.1 pmol/liter)] and SLV-HAs [43.2 +/- 13.3 pg/ml (112.3 +/- 34.6 pmol/liter)], but higher in SA-HAs [48.6 +/- 17.0 pg/ml (126.4 +/- 44.2 pmol/liter)]. After adjusting for gender and age within the site, two single nucleotide polymorphisms ( SNPs) in the vitamin D binding protein gene (DBP), rs4588 and rs7041, were associated with 25(OH) D, and one SNP in the DBP, rs4588, was associated with 1,25(OH)(2)D at all three study centers. Conclusions: SNPs in the DBP are associated with levels of 25(OH) D and 1,25(OH)(2)D in HA and AA participants in the Insulin Resistance Atherosclerosis Family Study.