Race, Ancestry, and Vitamin D Metabolism: The Multi-Ethnic Study of Atherosclerosis

Simon Hsu; Andrew N Hoofnagle; Deepak K Gupta; Orlando M Gutierrez; Carmen A Peralta; Steven Shea; Norrina B Allen; Gregory Burke; Erin D Michos; Joachim H Ix; David Siscovick; Bruce M Psaty; Karol E Watson; Bryan Kestenbaum; Ian H de Boer; Cassianne Robinson-Cohen

doi:10.1210/clinem/dgaa612

Race, Ancestry, and Vitamin D Metabolism: The Multi-Ethnic Study of Atherosclerosis

J Clin Endocrinol Metab. 2020 Dec 1;105(12):e4337-e4350. doi: 10.1210/clinem/dgaa612.

Authors

Simon Hsu¹, Andrew N Hoofnagle², Deepak K Gupta^{3

4}, Orlando M Gutierrez^{5

6}, Carmen A Peralta^{7

8

9}, Steven Shea^{10

11}, Norrina B Allen¹², Gregory Burke¹³, Erin D Michos^{14

15}, Joachim H Ix^{16

17}, David Siscovick¹⁸, Bruce M Psaty^{19

20}, Karol E Watson²¹, Bryan Kestenbaum¹, Ian H de Boer¹, Cassianne Robinson-Cohen^{22

23}

Affiliations

¹ Kidney Research Institute, Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington.
² Department of Laboratory Medicine, University of Washington, Seattle, Washington.
³ Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University Medical Center, Nashville, Tennessee.
⁴ Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
⁵ Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
⁶ Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama.
⁷ Cricket Health, Inc., San Francisco, California.
⁸ The Kidney Health Research Collaborative, San Francisco, California.
⁹ University of California, San Francisco, San Francisco, California.
¹⁰ Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York.
¹¹ Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
¹² Department of Internal Medicine, Northwestern University, Chicago, Illinois.
¹³ Division of Public Health Sciences Wake Forest School of Medicine, Winston-Salem, North Carolina.
¹⁴ Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
¹⁵ Department of Epidemiology and the Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
¹⁶ Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, California.
¹⁷ Division of Nephrology-Hypertension, University of California, San Diego, San Diego, California.
¹⁸ New York Academy of Medicine, New York, New York.
¹⁹ Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, Washington.
²⁰ Kaiser Permanente Washington Health Research Institute, Seattle, Washington.
²¹ Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California.
²² Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
²³ Vanderbilt Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, Tennessee.

Abstract

Context: A comprehensive characterization of racial/ethnic variations in vitamin D metabolism markers may improve our understanding of differences in bone and mineral homeostasis and the risk of vitamin D-related diseases.

Objective: Describe racial/ethnic differences in vitamin D metabolism markers and their associations with genetic ancestry.

Design, setting, participants: In a cross-sectional study within the Multi-Ethnic Study of Atherosclerosis (MESA), we compared a comprehensive panel of vitamin D metabolism markers across self-reported racial/ethnic groups of Black (N = 1759), White (N = 2507), Chinese (N = 788), and Hispanic (N = 1411). We evaluated associations of proportion African and European ancestry with this panel of markers in Black and Hispanic participants using ancestry informative markers. Latent class analysis evaluated associations between patterns of vitamin D measurements with race/ethnicity.

Results: Compared with Black participants, White participants had significantly higher serum concentrations of 25-hydroxyvitamin D and fibroblast growth factor-23; lower concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D; circulating vitamin D metabolite ratios suggesting lower CYP27B1 and higher CYP24A1 activity; higher urinary concentrations of calcium and phosphorus with higher urinary fractional excretion of phosphorus; and differences in vitamin D binding globulin haplotypes. Higher percent European ancestry was associated with higher 25-hydroxyvitamin D and lower parathyroid hormone concentrations among Black and Hispanic participants. Latent classes defined by vitamin D measurements reflected these patterns and differed significantly by race/ethnicity and ancestry.

Conclusions: Markers of vitamin D metabolism vary significantly by race/ethnicity, may serve to maintain bone and mineral homeostasis across ranges of 25-hydroxyvitamin D production, and be attributable, at least partly, to genetic ancestry.

Keywords: ancestry; mineral metabolism; parathyroid hormone; race; vitamin d.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Aged
Atherosclerosis* / ethnology
Atherosclerosis* / metabolism
Biomarkers / blood
Cohort Studies
Cross-Sectional Studies
Ethnicity / statistics & numerical data*
Female
Humans
Male
Middle Aged
Parathyroid Hormone / blood
Racial Groups / statistics & numerical data*
Risk Factors
United States / epidemiology
Vitamin D / analogs & derivatives
Vitamin D / blood
Vitamin D / metabolism*
Vitamin D Deficiency* / ethnology
Vitamin D Deficiency* / metabolism
Vitamin D-Binding Protein / blood

Substances

Biomarkers
Parathyroid Hormone
Vitamin D-Binding Protein
Vitamin D
25-hydroxyvitamin D

Abstract

Publication types

MeSH terms

Substances

Grants and funding