Introduction: The pathogenesis of Graves disease (GD) and Graves orbitopathy (GO) is not completely understood. On the other hand, vitamin D receptor (VDR) gene polymorphisms have been associated with susceptibility to a variety of chronic autoimmune diseases. The primary aim of this study was to synthesize the best available evidence regarding the association between VDR gene polymorphisms and risk of GD. Secondary aim was to search for their association with GO.
Methods/design: A comprehensive search was conducted in PubMed, CENTRAL and Scopus, up to December 8th, 2018. Data were expressed as odds ratio (OR) with 95% confidence intervals (CI). Heterogeneity was quantified with I2 index.
Results: Ten studies were included in the qualitative and quantitative analysis. TT subtype of TaqI polymorphism was associated with an increased risk of GD compared with Tt and tt polymorphisms (OR: 1.42; 95% CI, 1.051.94, P=0.025), whereas tt was associated with a lower risk of GD, compared with TT and Tt polymorphisms (OR: 0.79; 95% CI, 0.620.99, P=0.043). No association was found for ApaI, BsmI and FokI polymorphisms. When subgroup analysis was conducted according to ethnicity, a significant association was found for BsmI polymorphism and GD in both Asian (OR for the comparison of bb with the combination of BB plus Bb: 0.67; 95% CI, 0.490.92, P=0.013) and Caucasian populations (OR for bb compared with BB plus Bb:1.31, 95% CI, 1.041.65, P=0.022). Association was also found for TaqI polymorphism only in Caucasian population (OR for the comparison of tt with TT plus Tt: 0.74, 95% CI, 0.61-0.90, P=0.002). No eligible study was found regarding the association between VDR gene polymorphisms and the risk of GO.
Conclusions: The TT subtype of the TaqI polymorphism was associated with a higher susceptibility for GD compared with Tt and tt. Regarding BsmI, the bb subtype was associated with increased GD risk in Caucasians, whereas it is protective in Asians.
18 - 21 May 2019
European Society of Endocrinology