Vitamin D in Graves Disease: Levels, Correlation with Laboratory and Clinical Parameters, and Genetics

Abstract

Objective: The aim was to compare the vitamin D levels in patients with Graves disease (GD) with the general population and to correlate the vitamin D levels with laboratory and clinical parameters in GD. Moreover, we examined the genetic variation in genes involved in the vitamin D metabolism and their association with GD.

Methods: The levels of vitamin D were compared in 292 patients with newly diagnosed GD and 2,305 controls. Single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR), vitamin D binding protein (DBP), and 1-α-hydroxylase (CYP27B1) were examined for association with GD and/or Graves ophthalmopathy (GO) in 708 patients and 1,178 controls.

Results: Patients with GD had significantly lower vitamin D levels compared to controls (55.0 ± 23.2 vs. 87.2 ± 27.6 nmol/L, p < 0.001). In patients with GD (n = 219), there was no association between the levels of vitamin D at diagnosis and free thyroxine (fT₄), free triiodothyronine (fT₃), thyrotropin receptor antibodies (TRAb), GO at diagnosis, or relapse after terminating treatment with antithyroid drugs. Two SNPs in VDR were associated with GD: rs10735810 (OR = 1.36, 95% CI: 1.02-1.36, p = 0.02) and rs1544410 (OR = 1.47, 95% CI: 1.03-1.47, p = 0.02). There was no difference in the mean vitamin D level between genotypes in either rs10735810 or rs154410.

Conclusions: Patients with GD had lower vitamin D levels compared to the general population; however, the vitamin D levels did not affect the laboratory or clinical parameters of GD. SNPs in the VDR influenced the risk of GD through mechanisms other than reducing the vitamin D levels.

Keywords: Graves disease; Graves ophthalmopathy; Vitamin D; Vitamin D receptor.

Fig. 1

Vitamin D levels in controls (n = 2,305, 87.2 ± 27.6 nmol/L) and patients with Graves disease (n = 292, 55.0 ± 23.2 nmol/L, p < 0.0001)

Fig. 2

Prevalence of different vitamin D levels in patients with Graves disease (GD) and controls (<25 nmol/L: 7.5 vs. 0.3%, 26–50 nmol/L: 38.4 vs. 6.4%, 51–75 nmol/L: 33.2 vs. 27.9%, and >75 nmol/L: 20.9 vs. 65.5%, p < 0.0001).