Li Xin, Zhao Haixia, Xiao Zhifu
Department of Thyroid Surgery, Shanxi Provincial People's Hospital, 29 Shuangtasi Road, Taiyuan, 030012, Shanxi, China.
Department of Clinical Laboratory, General Hospital of Taiyuan Iron and Steel (Group) Company Limited, Taiyuan, 030003, Shanxi, China.
J Endocrinol Invest. 2025 Aug 9. doi: 10.1007/s40618-025-02666-6.
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.
Seven SNPs in the SPTLC1, ORMDL3, SPHK1, S1PR1 and S1PR3 were genotyped in 600 HT cases and 600 controls using a MassARRAY platform.
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.
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.
甲状腺滤泡破坏是桥本甲状腺炎（HT）的重要形态学表现，鞘脂（SPL）代谢对于维持膜脂质组成的稳态和细胞膜的稳定性至关重要。因此，HT的发病机制可能与SPL代谢有关。本研究旨在评估SPL代谢相关基因多态性与HT易感性之间的关联。
使用MassARRAY平台对600例HT患者和600例对照进行SPTLC1、ORMDL3、SPHK1、S1PR1和S1PR3基因的7个单核苷酸多态性（SNP）基因分型。
SPTLC1-rs11790991、SPHK1-rs346801和S1PR3-rs7022797的突变等位基因导致HT风险不同程度增加（p < 0.0001），而ORMDL3-rs8076131变异是HT发生的保护因素（p < 0.0001）。SPTLC1-rs11790991、SPHK1-rs346801和S1PR3-rs7022797突变杂合或纯合基因型携带者患HT的风险高于野生基因型携带者（p < 0.0001），而ORMDL3-rs8076131的突变AG/GG基因型导致HT易感性降低（p < 0.0001）。亚组分析表明，上述四个潜在的易感SNP在男性和女性中均保持显著差异。然而，这些显著相关性在不同遗传模型下表现不同。
这些结果有助于识别HT的高危人群，并表明研究SPL代谢可能是探索其发病机制的一个有前景的方向。
