Risk factors for vitamin D deficiency in sickle cell disease

Br J Haematol. 2018 Jun;181(6):828-835. doi: 10.1111/bjh.15270. Epub 2018 May 16.

Abstract

Vitamin D deficiency (VDD), 25-OHD levels <20 ng/ml, is prevalent among patients with sickle cell disease (SCD) and is linked to acute and chronic pain and bone fracture in this population. There is limited literature regarding VDD-associated risk factors for SCD. We examined potential clinical and genomic parameters associated with VDD in 335 adults with SCD in a cross-sectional study. VDD was present in 65% of adult SCD patients, and 25-OHD levels independently and positively correlated with older age (P < 0·001) and vitamin D supplementation (P < 0·001). 25-OHD levels were higher in SCD patients over 40 years of age compared to the general African-American population. Both lower 25-OHD levels and increased pain frequency were associated with increased expression of SLC6A5 encoding glycine transporter-2 (GlyT2), a protein involved in neuronal pain pathways. Lower 25-OHD levels were also associated with increased expression of CYP3A4, and with decreased expression of GC (also termed DBP) and VDR, three genes involved in vitamin D metabolism. We conclude that vitamin D supplementation should be an almost universal feature of the care of young adults with SCD, and that further research is warranted into genomic factors that regulate vitamin D metabolism in SCD.

Keywords: SLC6A5; gene expression; mortality; sickle; vitamin D.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Age Factors
  • Anemia, Sickle Cell* / drug therapy
  • Anemia, Sickle Cell* / genetics
  • Anemia, Sickle Cell* / metabolism
  • Cytochrome P-450 CYP3A / genetics
  • Cytochrome P-450 CYP3A / metabolism
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation
  • Glycine Plasma Membrane Transport Proteins / genetics
  • Glycine Plasma Membrane Transport Proteins / metabolism
  • Humans
  • Male
  • Mutation
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism
  • Registries
  • Risk Factors
  • Vitamin D / administration & dosage
  • Vitamin D / analogs & derivatives*
  • Vitamin D / pharmacokinetics
  • Vitamin D Deficiency* / drug therapy
  • Vitamin D Deficiency* / genetics
  • Vitamin D Deficiency* / metabolism

Substances

  • Glycine Plasma Membrane Transport Proteins
  • Receptors, Calcitriol
  • SLC6A5 protein, human
  • VDR protein, human
  • Vitamin D
  • 25-hydroxyvitamin D
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human