Association between cystatin C and Hashimoto thyroiditis: a clinical serological and Mendelian randomization study_West China Medical Journal

Authors：

CUI Bing ¹ ,  XU Chengcheng ²

1. Department of Transfusion Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P. R. China;
2. Department of Nuclear Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P. R. China;

Corresponding?author：

XU Chengcheng, Email: 1000012208@ujs.edu.cn

Keywords：

Hashimoto thyroiditis; cystatin C; causal relationship

DOI：

10.7507/1002-0179.202408341

Video：

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Objective To explore the association between cystatin C (CysC) and Hashimoto thyroiditis (HT), and to clarify the potential role of CysC in HT. Methods The newly diagnosed HT patients admitted to the Affiliated Hospital of Jiangsu University between January 2022 and December 2023 were selected as HT group and the same number of healthy physical examinees were selected as control group. The serum CysC levels of the two groups were compared. Subsequently, Mendelian randomization (MR) method (inverse variance weighted) was used to explore the association between CysC and HT. Results A total of 30 HT group patients and 30 healthy people were included. There was no significant difference in age and female proportion between HT group and control group (P>0.05). The serum CysC level in the HT group was higher than that in the control group [(0.91±0.16) vs. (0.79±0.11) mg/L, P<0.05]. MR analysis showed that higher serum CysC level would increase the risk of HT (P<0.05). The results of reverse MR analysis showed that there was no causal relationship between HT as an exposure factor and CysC as an outcome (P>0.05). Conclusion Clinical serological test results and MR analysis suggested that CysC may play an important role in the pathogenesis of HT.

Citation： CUI Bing, XU Chengcheng. Association between cystatin C and Hashimoto thyroiditis: a clinical serological and Mendelian randomization study. West China Medical Journal, 2025, 40(12): 1978-1981. doi: 10.7507/1002-0179.202408341 Copy

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2.	李自云, 莊新娟, 季業, 等. 黃芪對甲狀腺功能正常的橋本甲狀腺炎患者外周血 T 淋巴細胞亞群表達的影響. 上海交通大學學報(醫學版), 2024, 44(1): 108-115.
3.	Bastos DCDS, Chiamolera MI, Silva RE, et al. Metabolomic analysis of follicular fluid from women with Hashimoto thyroiditis. Sci Rep, 2023, 13(1): 12497.
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5.	Osowiecka K, Myszkowska-Ryciak J. The influence of nutritional intervention in the treatment of Hashimoto’s thyroiditis-a systematic review. Nutrients, 2023, 15(4): 1041.
6.	Qin Q, Yang M, Ke W, et al. Serum cystatin C is closely associated with euthyroid Hashimoto’s thyroiditis in adult female Chinese patients. J Int Med Res, 2020, 48(8): 300060520952973.
7.	Mottaghi A, Alipour F, Alibeik N, et al. Serum cystatin C and inflammatory factors related to COVID-19 consequences. BMC Infect Dis, 2023, 23(1): 339.
8.	Huang H, Zhang Y, Gui L, et al. Proteomic analyses reveal cystatin c is a promising biomarker for evaluation of systemic lupus erythematosus. Clin Proteomics, 2023, 20(1): 43.
9.	S?bü E, Yildiz Z. Does cystatin C have an immunomodulatory role in Hashimoto’s thyroiditis?. J Pediatr Endocrinol Metab, 2022, 36(1): 58-63.
10.	Pan Y, Zhang J, He T. SARS-CoV-2 neurovascular invasion supported by Mendelian randomization. J Transl Med, 2024, 22(1): 101.
11.	Simistiras A, Georgiopoulos G, Delialis D, et al. Association of lipoprotein(a) with arterial stiffness: a Mendelian randomization study. Eur J Clin Invest, 2024, 54(5): e14168.
12.	Chen LG, Tubbs JD, Liu Z, et al. Mendelian randomization: causal inference leveraging genetic data. Psychol Med, 2024, 54(8): 1461-1474.
13.	吳娜, 魏爽, 師新雨, 等. 孟德爾隨機化在流行病學中的優勢與應用: 以多囊卵巢綜合征相關激素與代謝功能障礙相關脂肪性肝病的因果關系為例. 數理醫藥學雜志, 2025, 38(5): 315-321.
14.	中華醫學會內分泌學分會. 中國甲狀腺疾病診治指南——甲狀腺炎. 中華內科雜志, 2008, 47(9): 784-788.
15.	丁韻涵, 張莎莎, 趙曉曉, 等. 輻射暴露與頭頸癌風險的因果關聯: 孟德爾隨機化研究. 華西醫學, 2025, 40(7): 1124-1127.
16.	Xin C, Xie J, Fan H, et al. Association between serum cystatin C and thyroid diseases: a systematic review and meta-analysis. Front Endocrinol (Lausanne), 2021, 12: 766516.
17.	Tillmann FP, Harth A, J?rres A. Hashimoto’s thyroiditis-associated acute renal failure and pitfalls of eGFR interpretation in thyroid diseases. Eur J Case Rep Intern Med, 2021, 8(7): 002645.
18.	Yang W, Yang Y, He L, et al. Dietary factors and risk for asthma: a Mendelian randomization analysis. Front Immunol, 2023, 14: 1126457.
19.	Wang Y, Guo J, Ni G, et al. Theoretical and empirical quantification of the accuracy of polygenic scores in ancestry divergent populations. Nat Commun, 2020, 11(1): 3865.
20.	Zi M, Xu Y. Involvement of cystatin C in immunity and apoptosis. Immunol Lett, 2018, 196: 80-90.
21.	Hunaiti S, Wallin H, Eriksson M, et al. Secreted cystatins decrease proliferation and enhance apoptosis of human leukemic cells. FEBS Open Bio, 2020, 10(10): 2166-2181.
22.	Gren ST, Janciauskiene S, Sandeep S, et al. The protease inhibitor cystatin C down-regulates the release of IL-β and TNF-α in lipopolysaccharide activated monocytes. J Leukoc Biol, 2016, 100(4): 811-822.
23.	Padia G, Mahajan B, Kumar A, et al. Cystatin C and interleukin-6 for prognosticating patients with acute decompensation of cirrhosis. JGH Open, 2021, 5(4): 459-464.

1. Upreti A, Mukherjee S. Therapeutic potential of CRISPR/Cas in Hashimoto’s thyroiditis: a comprehensive review. Curr Gene Ther, 2024, 24(3): 179-192.
2. 李自云, 莊新娟, 季業, 等. 黃芪對甲狀腺功能正常的橋本甲狀腺炎患者外周血 T 淋巴細胞亞群表達的影響. 上海交通大學學報(醫學版), 2024, 44(1): 108-115.
3. Bastos DCDS, Chiamolera MI, Silva RE, et al. Metabolomic analysis of follicular fluid from women with Hashimoto thyroiditis. Sci Rep, 2023, 13(1): 12497.
4. Ata? PK. A novel hybrid model to predict concomitant diseases for Hashimoto’s thyroiditis. BMC Bioinformatics, 2023, 24(1): 319.
5. Osowiecka K, Myszkowska-Ryciak J. The influence of nutritional intervention in the treatment of Hashimoto’s thyroiditis-a systematic review. Nutrients, 2023, 15(4): 1041.
6. Qin Q, Yang M, Ke W, et al. Serum cystatin C is closely associated with euthyroid Hashimoto’s thyroiditis in adult female Chinese patients. J Int Med Res, 2020, 48(8): 300060520952973.
7. Mottaghi A, Alipour F, Alibeik N, et al. Serum cystatin C and inflammatory factors related to COVID-19 consequences. BMC Infect Dis, 2023, 23(1): 339.
8. Huang H, Zhang Y, Gui L, et al. Proteomic analyses reveal cystatin c is a promising biomarker for evaluation of systemic lupus erythematosus. Clin Proteomics, 2023, 20(1): 43.
9. S?bü E, Yildiz Z. Does cystatin C have an immunomodulatory role in Hashimoto’s thyroiditis?. J Pediatr Endocrinol Metab, 2022, 36(1): 58-63.
10. Pan Y, Zhang J, He T. SARS-CoV-2 neurovascular invasion supported by Mendelian randomization. J Transl Med, 2024, 22(1): 101.
11. Simistiras A, Georgiopoulos G, Delialis D, et al. Association of lipoprotein(a) with arterial stiffness: a Mendelian randomization study. Eur J Clin Invest, 2024, 54(5): e14168.
12. Chen LG, Tubbs JD, Liu Z, et al. Mendelian randomization: causal inference leveraging genetic data. Psychol Med, 2024, 54(8): 1461-1474.
13. 吳娜, 魏爽, 師新雨, 等. 孟德爾隨機化在流行病學中的優勢與應用: 以多囊卵巢綜合征相關激素與代謝功能障礙相關脂肪性肝病的因果關系為例. 數理醫藥學雜志, 2025, 38(5): 315-321.
14. 中華醫學會內分泌學分會. 中國甲狀腺疾病診治指南——甲狀腺炎. 中華內科雜志, 2008, 47(9): 784-788.
15. 丁韻涵, 張莎莎, 趙曉曉, 等. 輻射暴露與頭頸癌風險的因果關聯: 孟德爾隨機化研究. 華西醫學, 2025, 40(7): 1124-1127.
16. Xin C, Xie J, Fan H, et al. Association between serum cystatin C and thyroid diseases: a systematic review and meta-analysis. Front Endocrinol (Lausanne), 2021, 12: 766516.
17. Tillmann FP, Harth A, J?rres A. Hashimoto’s thyroiditis-associated acute renal failure and pitfalls of eGFR interpretation in thyroid diseases. Eur J Case Rep Intern Med, 2021, 8(7): 002645.
18. Yang W, Yang Y, He L, et al. Dietary factors and risk for asthma: a Mendelian randomization analysis. Front Immunol, 2023, 14: 1126457.
19. Wang Y, Guo J, Ni G, et al. Theoretical and empirical quantification of the accuracy of polygenic scores in ancestry divergent populations. Nat Commun, 2020, 11(1): 3865.
20. Zi M, Xu Y. Involvement of cystatin C in immunity and apoptosis. Immunol Lett, 2018, 196: 80-90.
21. Hunaiti S, Wallin H, Eriksson M, et al. Secreted cystatins decrease proliferation and enhance apoptosis of human leukemic cells. FEBS Open Bio, 2020, 10(10): 2166-2181.
22. Gren ST, Janciauskiene S, Sandeep S, et al. The protease inhibitor cystatin C down-regulates the release of IL-β and TNF-α in lipopolysaccharide activated monocytes. J Leukoc Biol, 2016, 100(4): 811-822.
23. Padia G, Mahajan B, Kumar A, et al. Cystatin C and interleukin-6 for prognosticating patients with acute decompensation of cirrhosis. JGH Open, 2021, 5(4): 459-464.

West China Medical Journal

Association between cystatin C and Hashimoto thyroiditis: a clinical serological and Mendelian randomization study

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