Genome-wide association study of vitamin D concentrations and bone mineral density in the African American-Diabetes Heart Study.

Genome-wide association study of vitamin D concentrations and bone mineral density in the African American-Diabetes Heart Study.

Relative to European Americans, African Americans have lower 25-hydroxyvitamin D (25OHD) and vitamin D binding protein (VDBP) concentrations, higher 1,25-dihydroxyvitamin D (1,25(OH)2D3) concentrations and bone mineral density (BMD), and paradoxically reduced burdens of calcified atherosclerotic pla...

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Autores principales: Nicholette D Palmer, Lingyi Lu, Thomas C Register, Leon Lenchik, J Jeffrey Carr, Pamela J Hicks, S Carrie Smith, Jianzhao Xu, Latchezar Dimitrov, Jacob Keaton, Meijian Guan, Maggie C Y Ng, Yii-der I Chen, Anthony J Hanley, Corinne D Engelman, Jill M Norris, Carl D Langefeld, Lynne E Wagenknecht, Donald W Bowden, Barry I Freedman, Jasmin Divers
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2021
Materias:
Medicine
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Science
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Acceso en línea:https://doaj.org/article/1db08e71b48b43f89880d407c287f360
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Sumario:Relative to European Americans, African Americans have lower 25-hydroxyvitamin D (25OHD) and vitamin D binding protein (VDBP) concentrations, higher 1,25-dihydroxyvitamin D (1,25(OH)2D3) concentrations and bone mineral density (BMD), and paradoxically reduced burdens of calcified atherosclerotic plaque (subclinical atherosclerosis). To identify genetic factors contributing to vitamin D and BMD measures, association analysis of >14M variants was conducted in a maximum of 697 African American-Diabetes Heart Study participants with type 2 diabetes (T2D). The most significant association signals were detected for VDBP on chromosome 4; variants rs7041 (β = 0.44, SE = 0.019, P = 9.4x10-86) and rs4588 (β = 0.17, SE = 0.021, P = 3.5x10-08) in the group-specific component (vitamin D binding protein) gene (GC). These variants were found to be independently associated. In addition, rs7041 was also associated with bioavailable vitamin D (BAVD; β = 0.16, SE = 0.02, P = 3.3x10-19). Six rare variants were significantly associated with 25OHD, including a non-synonymous variant in HSPG2 (rs116788687; β = -1.07, SE = 0.17, P = 2.2x10-10) and an intronic variant in TNIK (rs143555701; β = -1.01, SE = 0.18, P = 9.0x10-10), both biologically related to bone development. Variants associated with 25OHD failed to replicate in African Americans from the Insulin Resistance Atherosclerosis Family Study (IRASFS). Evaluation of vitamin D metabolism and bone mineral density phenotypes in an African American population enriched for T2D could provide insight into ethnic specific differences in vitamin D metabolism and bone mineral density.

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