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Genetic and Environmental Determinants of 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Levels in Hispanic and African Americans

Department of Population Health Sciences (C.D.E.), University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53726-2397; Department of Preventive Medicine and Biometrics (T.E.F., J.M.N.), University of Colorado at Denver and Health Sciences Center, Denver, Colorado 80217-3364; Departments of Public Health Sciences (C.D.L., L.E.W.) and Biochemistry and Center for Human Genomics (P.J.H., D.W.B.), Wake Forest University School of Medicine, Winston Salem, North Carolina 27103; and Department of Public Health Sciences (S.S.R.), University of Virginia School of Medicine, Charlottesville, Virginia 22908

Address all correspondence and requests for reprints to: Corinne D. Engelman, Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, 610 Walnut Street, 1007A WARF, Madison, Wisconsin 53726-2397. E-mail: cengelman{at}wisc.edu.

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)₂D] 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)₂D 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)₂D 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)₂D at all three study centers.

Conclusions: SNPs in the DBP are associated with levels of 25(OH)D and 1,25(OH)₂D in HA and AA participants in the Insulin Resistance Atherosclerosis Family Study.