Vitamin D status and variable responses to supplements depend in part on genetic factors in adults with cystic fibrosis

Andrew T Braun; HuiChuan J Lai; Anita Laxova; Julie A Biller; Erin K Hubertz; Zijie Zhao; Qiongshi Lu; Sangita Murali; Donna M Brown; Elizabeth A Worthey; Philip M Farrell

doi:10.1016/j.jcf.2024.02.005

Vitamin D status and variable responses to supplements depend in part on genetic factors in adults with cystic fibrosis

J Cyst Fibros. 2024 Feb 20:S1569-1993(24)00020-1. doi: 10.1016/j.jcf.2024.02.005. Online ahead of print.

Authors

Affiliations

¹ Department of Medicine, University of Wisconsin, Madison WI, USA. Electronic address: atbraun@medicine.wisc.edu.
² Department of Pediatrics, University of Wisconsin, Madison WI, USA; Department of Nutritional Sciences, University of Wisconsin, Madison WI, USA.
³ Department of Pediatrics, University of Wisconsin, Madison WI, USA.
⁴ Department of Medicine, Medical College of Wisconsin, Milwaukee WI, USA.
⁵ Department of Statistics, University of Wisconsin, Madison WI, USA; Department of Biostatistics & Medical Informatics, University of Wisconsin, Madison, WI, USA.
⁶ Department of Nutritional Sciences, University of Wisconsin, Madison WI, USA.
⁷ Department of Genetics, Center for Computational Genomics and Data Science at the University of Alabama Birmingham, Marnix E. Heersink School of Medicine, Birmingham, AL, USA.

PMID: 38383231
DOI: 10.1016/j.jcf.2024.02.005

Abstract

Vitamin D sufficiency has been difficult to achieve consistently in patients with cystic fibrosis (CF), even with robust oral supplements. To assess vitamin D status and resistance to supplementation, we studied 80 adults using 25-hydroxyvitamin D (25OHD) determinations and whole genome sequencing to construct polygenic risk scores (PRS) that aggregate variants associated with vitamin D status. The results revealed that 30 % of patients were below the threshold of 30 ng/mL and thus should be regarded as insufficient despite normal vitamin E status, a reflection of adherence to fat soluble vitamin supplementation. The PRS values were significantly correlated with 25OHD concentrations, confirming our results in children with CF, and indicating that genetic factors play a role and have implications for therapy.

Keywords: 25-hydroxyvitamin D; Cystic fibrosis; Polygenic risk score; Single nucleotide polymorphism; Vitamin D supplementation; Whole genome sequencing.