Presentation Type

Poster Presentation

Category

STEM (science, technology, engineering, mathematics)

Abstract/Artist Statement

Purpose: Vitamin D is an essential hormone in maintenance of calcium and phosphate homeostasis for adequate bone mineralization with roles in the immune system as well. Sources of vitamin D include natural synthesis in the skin upon ultraviolet B (UVB) radiation, dietary intake from plant and animal sources, and supplementation. Vitamin D levels, measured by the primary circulating vitamin D metabolite, 25-hydroxyvitamin D (25(OH)D), are variable across individuals due to latitude, season, diet, gender, disease states, medication use, and genetics. Populations living at northern latitudes (~400N) such as American Indians of the Confederated Salish and Kootenai Tribes (CSKT) are at increased susceptibility of having lower vitamin D levels in the winter months because there is decreased UVB exposure. There are currently no published data that exist on the genetic and seasonal influence on vitamin D status in CSKT people. Methods: We recruited 472 research participants from the Confederated Salish and Kootenai Tribes (CSKT) (185 male and 287 female; 18 years or older) at various sites in the Flathead Reservation in western Montana. Demographic factors were collected (e.g., age, body mass index, and gender). Genomic DNA and plasma were isolated from whole blood. We sequenced 12 candidate genes: 7-dehydrocholesterol reductase (DHCR7), calcium-sensing receptor (CASR), cubulin (CUBN), cytochrome P450 enzymes (CYP2R1, CYP27B1, CYP24A1, and CYP3A4), retinoid X receptors (RXR alpha, beta, and gamma), sulfotransferase family 2A member 1 (SULT2A1), UDP-glucuronosyltransferase family 1A3 and 1A4 (UGT1A3 and UGT1A4), vitamin D binding protein (GC), and vitamin D receptor (VDR). We also measured circulating levels of vitamin D and metabolites: vitamin D3 and vitamin D2, 25-hydroxyvitamin D [25(OH)D3 and 25(OH)D2], 1,25-dihydroxyvitamin D3 and D2 [1,25(OH)2D3 and 1,25(OH)2D2], 24R,25-dihydroxyvitamin D3 [24R,25(OH)D3], and 4-b,25-dihydroxyvitamin D3 [4b,25(OH)2D3]. Candidate genes were resequenced with Illumina next generation sequencing technology and vitamin D and metabolites were quantitated with liquid chromatography mass spectrometry (LC-MS/MS). The data we collected was summarized using a pipeline state of the art bioinformatics software. Originality: This research addresses the need for increased inclusion of American Indian and Alaska Natives in precision medicine health research. We have characterized genetic variation in vitamin D endocrinology genes and seasonal variability in vitamin D and vitamin D metabolite levels for the first time in CSKT people. Significance: We observed known and novel genetic variation in the CSKT population based on the presence or absence of genetic variants in the National Center for Biotechnology Information (NCBI) Single Nucleotide Polymorphism Database (dbSNP). We observed clinically relevant genetic variants that are associated with disease and variability in response to medication based on presence in the NCBI ClinVar and Pharmacogenomics Knowledge Base (PharmGKB) databases. Vitamin D and metabolite levels varied in a seasonal, fluctuating way, as expected, with lowest levels in January, February, and March months and highest levels in June, July, and August months. A significant percentage of CSKT participants had measured vitamin D levels below sufficiency (~43%). We will use these data to design an interventional strategy to address the low vitamin D levels we observed in CSKT people.

Mentor Name

Erica Woodahl

Personal Statement

The lack of inclusion of American Indian and Alaska Native communities such as the Confederated Salish and Kootenai Tribes (CSKT) on the Flathead Reservation in Montana in precision medicine and pharmacogenomics research is a current healthcare disparity that needs to be addressed. In Montana, healthcare disparities are striking in tribal and rural communities. Since there is currently little or no precision medicine and pharmacogenomics research knowledge available for these populations, they are at risk of not benefiting from health innovations that arise from this research, potentially exacerbating healthcare disparities. By increasing participation of these groups in precision medicine research often, researchers and doctors can identify unique individual characteristics (e.g., genes, environment, and lifestyle) that influence how they respond to medications and use this knowledge to improve healthcare for these underserved communities. This work provides the value of increased inclusion of the CSKT people, an underserved and understudied population, in precision medicine research. In the long term, this research with the CSKT will generate novel data on seasonal vitamin D levels and associations with genetic variation in genes of the vitamin D endocrine system. The data from this research will provide knowledge to the field of precision medicine and pharmacogenomics that can be potentially be used to optimize clinical care in CSKT people.

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Genetic and seasonal contributions to variability in vitamin D levels among American Indians

Purpose: Vitamin D is an essential hormone in maintenance of calcium and phosphate homeostasis for adequate bone mineralization with roles in the immune system as well. Sources of vitamin D include natural synthesis in the skin upon ultraviolet B (UVB) radiation, dietary intake from plant and animal sources, and supplementation. Vitamin D levels, measured by the primary circulating vitamin D metabolite, 25-hydroxyvitamin D (25(OH)D), are variable across individuals due to latitude, season, diet, gender, disease states, medication use, and genetics. Populations living at northern latitudes (~400N) such as American Indians of the Confederated Salish and Kootenai Tribes (CSKT) are at increased susceptibility of having lower vitamin D levels in the winter months because there is decreased UVB exposure. There are currently no published data that exist on the genetic and seasonal influence on vitamin D status in CSKT people. Methods: We recruited 472 research participants from the Confederated Salish and Kootenai Tribes (CSKT) (185 male and 287 female; 18 years or older) at various sites in the Flathead Reservation in western Montana. Demographic factors were collected (e.g., age, body mass index, and gender). Genomic DNA and plasma were isolated from whole blood. We sequenced 12 candidate genes: 7-dehydrocholesterol reductase (DHCR7), calcium-sensing receptor (CASR), cubulin (CUBN), cytochrome P450 enzymes (CYP2R1, CYP27B1, CYP24A1, and CYP3A4), retinoid X receptors (RXR alpha, beta, and gamma), sulfotransferase family 2A member 1 (SULT2A1), UDP-glucuronosyltransferase family 1A3 and 1A4 (UGT1A3 and UGT1A4), vitamin D binding protein (GC), and vitamin D receptor (VDR). We also measured circulating levels of vitamin D and metabolites: vitamin D3 and vitamin D2, 25-hydroxyvitamin D [25(OH)D3 and 25(OH)D2], 1,25-dihydroxyvitamin D3 and D2 [1,25(OH)2D3 and 1,25(OH)2D2], 24R,25-dihydroxyvitamin D3 [24R,25(OH)D3], and 4-b,25-dihydroxyvitamin D3 [4b,25(OH)2D3]. Candidate genes were resequenced with Illumina next generation sequencing technology and vitamin D and metabolites were quantitated with liquid chromatography mass spectrometry (LC-MS/MS). The data we collected was summarized using a pipeline state of the art bioinformatics software. Originality: This research addresses the need for increased inclusion of American Indian and Alaska Natives in precision medicine health research. We have characterized genetic variation in vitamin D endocrinology genes and seasonal variability in vitamin D and vitamin D metabolite levels for the first time in CSKT people. Significance: We observed known and novel genetic variation in the CSKT population based on the presence or absence of genetic variants in the National Center for Biotechnology Information (NCBI) Single Nucleotide Polymorphism Database (dbSNP). We observed clinically relevant genetic variants that are associated with disease and variability in response to medication based on presence in the NCBI ClinVar and Pharmacogenomics Knowledge Base (PharmGKB) databases. Vitamin D and metabolite levels varied in a seasonal, fluctuating way, as expected, with lowest levels in January, February, and March months and highest levels in June, July, and August months. A significant percentage of CSKT participants had measured vitamin D levels below sufficiency (~43%). We will use these data to design an interventional strategy to address the low vitamin D levels we observed in CSKT people.