Association of the CASQ1 Gene SNP rs3838216 with Graves’ Ophthalmopathy and Hashimoto’s Thyroiditis in Patients with Thyroid Autoimmunity

The pathogenesis of Graves’ ophthalmopathy is poorly understood, but there is evidence for the involvement of calsequestrin (CASQ1) as an autoantigen.

Aim: To compare the frequency of the single nucleotide polymorphism (SNP) rs3838216 (located in intron 1 of CASQ1) in patients with autoimmune thyroid disease (ATD), Graves’ Ophthalmopathy and controls.

Methods: Germline DNA was assayed for rs3838216 by MassARRAY SNP analysis using iPLEX technology of SEQUENOM in 405 individuals (98 males, 307 females) with ATD (comprising Graves’ Opthalmopathy (GO, N=74), Graves’ Hyperthyroidism (GH, N=131), Hashimoto’s thyroiditis (HT, N=92), and controls with no personal or family history of autoimmune thyroid disorders (N=108).

Results: Genotypes for rs3838216 differed significantly across groups with minor allele frequencies as follows: GO 17%, GH 24%, HT 19% and controls 30% groups (P=0.0427). P of SNP rs3838216 was significant in GO vs. control (odds ratio 2.16, P=0.003), and HT vs control (odds ratio 1.87, P= 0.008). On pair wise analysis, homozygosity for the major allele was associated with GO vs. control (odds ratio = 2.42, P=0.0046), and HT vs control (odds ratio 2.07, P=0.0116); whereas heterozygosity was associated with GO vs. control (odds ratio = 0.52, P=0.039), and HT vs control (odds ratio 0.570, P=0.054).

Conclusion: The CASQ1 gene SNP rs3838216 is associated with autoimmune thyroid disease and with GO in particular.