Effects of sphingolipid metabolism related genes-SPTLC1, ORMDL3, SPHK1 and S1PR3 polymorphisms on susceptibility to hashimoto's thyroiditis.

Background: The destruction of thyroid follicles is an important morphological manifestation of Hashimoto's thyroiditis (HT), and sphingolipid (SPL) metabolism is crucial for maintaining the homeostasis of membrane lipid composition and the stability of the cell membrane. Therefore, the pathogenesis of HT may be related to SPL metabolism. This study aimed to evaluate the associations between SPL metabolism related genes polymorphisms and susceptibility to HT.

Methods: Seven SNPs in the SPTLC1, ORMDL3, SPHK1, S1PR1 and S1PR3 were genotyped in 600 HT cases and 600 controls using a MassARRAY platform.

Results: The mutation alleles of SPTLC1-rs11790991, SPHK1-rs346801 and S1PR3-rs7022797 led to varying degrees of increased HT risk (p < 0.0001), while the ORMDL3-rs8076131 variant was a protective factor for developing HT (p < 0.0001). Carriers of the mutant heterozygous or homozygous genotypes of SPTLC1-rs11790991, SPHK1-rs346801 and S1PR3-rs7022797 exhibited higher risk of HT than those carrying the wild genotypes (p < 0.0001), while the mutant AG/GG genotypes of ORMDL3-rs8076131 resulted in a reduction in HT susceptibility (p < 0.0001). Subgroup analysis showed that the above four potential susceptible SNPs maintained significant in both males and females. However, these significant correlations are manifested under different genetic models.

Conclusions: These results can help identify high-risk populations for HT and suggest that studying SPL metabolism may be a promising direction to explore its pathogenesis.