A novel FoxD3 variant is associated with vitiligo and elevated thyroid auto-antibodies.

A novel FoxD3 variant is associated with vitiligo and elevated thyroid auto-antibodies.

J Clin Endocrinol Metab. 2015 Aug 12;:jc20152126

Authors: Schunter JA, Löffler D, Wiesner T, Kovacs P, Badenhoop K, Aust G, Tönjes A, Müller P, Baber R, Simon JC, Führer D, Pfäffle RW, Thiery J, Stumvoll M, Kiess W, Kratzsch J, Körner A

Abstract
CONTEXT: Vitiligo frequently coincides with autoimmune endocrinopathies, particularly Hashimoto´s thyroiditis (HT). Genetic susceptibility may underlie this coincident occurrence. One candidate region is the autoimmunity susceptibility locus on chromosome 1, which encompasses FoxD3, a gene involved in embryonal melanogenesis. We identified a promotor variant (rs78645479) in an index case of vitiligo+HT+candidiasis and evaluated its clinical and functional relevance.
DESIGN: We genotyped 281 patients with variable autoimmune endocrinopathies: HT, Graves´disease (GD), type 1 diabetes (T1D), Addison´s disease (AD), autoimmune polyglandular syndrome (APS) and/or vitiligo and 1858 controls. Furthermore, we assessed the effect of the variant on promotor activity and assessed the expression of FoxD3 in thyroid tissue samples.
RESULTS: Patients with vitiligo had a higher frequency of the risk allele (30%) compared to healthy controls (18.2%). In addition, the variant was associated with the incidence of elevated anti-TPO antibodies and anti-Tg antibodies, but not with TSH, FT3 or FT4 levels and also not with GD, T1D, AD or APS. Functionally, the variant increased transcriptional activity in Jurkat and in Hek293 cells. We confirmed gene expression of FoxD3 in human thyroid tissue, which appeared elevated in thyroid tissue samples of patients with GD and non-autoimmune goiter, but not in patients with HT.
CONCLUSION: In addition to a possible association of rs78645479 in FoxD3 with vitiligo, our data on the association of this FoxD3 variant with thyroid autoantibodies suggest a potential involvement of FoxD3 in thyroid immunoregulation.

PMID: 26267147 [PubMed - as supplied by publisher]