Prevalence of vitamin D deficiency in women from southern Brazil and association with vitamin D-binding protein levels and GC-DBP gene polymorphisms

PLoS One. 2019 Dec 12;14(12):e0226215. doi: 10.1371/journal.pone.0226215. eCollection 2019.


Vitamin D deficiency is highly prevalent worldwide, and vitamin D-binding protein (DBP) a major regulator of serum vitamin D levels. The rs4588 and rs7041 polymorphisms of the GC gene constitute the genetic basis of the three major isoforms of circulating DBP (GC1s, GC1f, and GC2), while the rs2282679 variant is located in an important regulatory region of the GC gene. The aim of this study was to assess the prevalence of 25-hydroxyvitamin D [25(OH)D] deficiency and to ascertain whether it is associated with DBP levels and with GC gene variants. Biorepository samples of 443 women aged 20 to 72 years, with no evidence of clinical disease, were analyzed. Circulating levels of 25(OH)D were considered sufficient if ≥20 ng/mL and deficient if <20 ng/mL. Genotype analysis was performed by RT-PCR. Mean age was 53.4±9.4 years; mean BMI was 27.8±5.8 kg/m2. The overall sample had mean 25(OH)D levels of 22.8±8.3 ng/mL; 39.7% of participants had deficient circulating 25(OH)D levels. Higher prevalence ratios (PR) of 25(OH)D deficiency were found for the CC genotype of rs2282679 (PR 1.74; 95%CI 1.30 to 2.24; p<0.001), GC2 isoform (PR 1.66; 95%CI 1.17 to 2.38; p = 0.005), time since menopause (PR 1.02; 95%CI 1.003 to 1.03, p = 0.016), and HOMA-IR (PR 1.02; 95%CI 1.01 to 1.03, p = 0.004). DBP levels (per 30 μg/mL increase in DBP) were associated with lower PR for 25(OH)D deficiency (PR 0.89; 95%CI 0.80;0.99; p = 0.027). Except for HOMA-IR, these prevalence ratios remained significant after adjustment for age and BMI. In conclusion, the rs2282679 polymorphism and the GC2 isoform of DBP were associated with lower serum DBP levels and with susceptibility to 25(OH)D deficiency in Brazilian women with no evidence of clinical disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Brazil / epidemiology
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Prevalence
  • Risk Factors
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / epidemiology*
  • Vitamin D Deficiency / genetics
  • Vitamin D-Binding Protein / blood*
  • Vitamin D-Binding Protein / genetics
  • Young Adult


  • GC protein, human
  • Vitamin D-Binding Protein
  • Vitamin D
  • 25-hydroxyvitamin D

Grants and funding

This work was supported by: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq INCT 465482/2014-7); Fundação de Amparo à Pesquisa do Rio Grande do Sul (FAPERGS INCT 17/2551-0000519-8) to PMS. This work was also supported by a Post-doctoral grant, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES PNPD-008898340001-08) to BRS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.