Vitamin D receptor polymorphisms are associated with Graves' disease in German and Polish but not in Serbian patients.

Diverse genes are candidates for susceptibility to Graves' disease, including the vitamin D receptor (VDR), which regulates the transcription of target genes in response to the active metabolite 1,25(OH)(2)D(3). We analyzed four polymorphisms of the VDR gene (ApaI, TaqI, BsmI, and FokI) in patients with Graves' disease (n = 789) and healthy controls (n = 823) from three European populations (German, Polish, and Serbian). The VDR ApaI (rs7975232) and TaqI (rs731236) polymorphisms showed no significant difference in any population. The BsmI (rs1544410) variant "b" was associated with Graves' disease in the Polish population (p = 0.0070). The FokI (rs10735810) variant "f " was found to be associated with Graves' disease in Germans and "F" in Polish patients (p = 0.0024 and 0.0049, respectively). Construction of haplotypes for TaqI, ApaI, and BsmI showed the haplotype "Tab" to be the most frequent in the German and Polish population as well as in the Serbian patients, while "tAB" in Serbian controls. Our results show an association of VDR gene polymorphisms in the German and Polish population but not in the Serbian. Furthermore, the VDR polymorphisms are differentially distributed in the three populations. Therefore, VDR polymorphisms analysis needs to be stratified according to the population background.