# Vitamin D Genetics and Racial Differences in Pediatric Chronic Kidney Disease-Mineral and Bone Disorder

> **NIH NIH K23** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $205,753

## Abstract

PROJECT SUMMARY
This is an initial submission of a K23 application by Dr. Marciana Laster from the University of California, Los
Angeles (UCLA). Candidate: Dr. Laster’s training objectives in this proposal include to: 1) develop expertise in
the physiology and genetics of the PTH-Vitamin D axis, 2) gain further skills in the management of
epidemiologic data, principles of genetic association studies and advanced bio-statistical approaches and 3)
develop expertise in the assessment of bone turnover by bone histomorphometry. Dr. Laster will accomplish
these activities through mentorship, coursework and participation in workshops. She has assembled a team of
scientists including her primary mentor Dr. Isidro Salusky, an expert in pediatric CKD-MBD and co-mentor Dr.
Ravi Thadhani, an expert in Vitamin D metabolism. Research: Pediatric CKD-MBD affects nearly all pediatric
patients with CKD by the time they reach dialysis. Despite years of treatment with active Vitamin D sterols,
skeletal morbidity and cardiovascular mortality remain unacceptably high. Dr. Laster’s long-term goal is to
individualize the treatment of pediatric CKD-MBD in order to improve the health and quality of life of pediatric
CKD patients. The first step toward accomplishing this goal involves the identification of genetic variants that
predict PTH levels and skeletal response to PTH levels. Dr. Laster hypothesizes that the risk of secondary
hyperparathyroidism and the degree of PTH responsiveness in CKD are predicted by genetic variation in the
Vitamin D Receptor (VDR) gene, which mediates PTH release and osteoclast activity, and the Vitamin D
Binding Protein (VDBP) gene, which mediates vitamin D transport and osteoclast activity. In Dr. Laster’s
preliminary work she demonstrated clinical outcomes suggestive of underlying PTH resistance amongst
African-Americans. A genetic basis of this PTH resistance is supported by studies demonstrating select genetic
variants found frequently amongst African-Americans which are associated with a clinical picture suggestive of
PTH resistance. In Aim 1, Dr. Laster will identify SNPs within the VDR and VDBP genes that explain variation
in PTH levels using a pre-dialysis CKD cohort of 1076 patients and a dialysis cohort of 100 patients. This aim
will establish how SNPs in the VDR and VDBP associate with serum PTH levels in the pediatric CKD
population. In Aim 2, Dr. Laster will identify SNPs in the VDR and VDBP that explain variation in PTH-adjusted
bone turnover. This aim will establish SNPs that are associated with a variable response of bone to elevations
in PTH (i.e. PTH resistance). In Aim 3, Dr. Laster will perform a genome wide association study in the 1076
pediatric pre-dialysis CKD patients in order to identify novel SNPs that explain variation in PTH levels. Dr.
Laster’s aims will help to establish a phenotype of skeletal response that can then be used to individualize the
intensity of pediatric CKD-MBD therapy.

## Key facts

- **NIH application ID:** 9872008
- **Project number:** 1K23DK123378-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Marciana Lee Laster
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $205,753
- **Award type:** 1
- **Project period:** 2020-07-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9872008

## Citation

> US National Institutes of Health, RePORTER application 9872008, Vitamin D Genetics and Racial Differences in Pediatric Chronic Kidney Disease-Mineral and Bone Disorder (1K23DK123378-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9872008. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*