Polymorphisms of ATG5 Gene Are Associated with Autoimmune Thyroid Diseases, Especially Thyroid Eye Disease

Overview

Journal J Immunol Res

Publisher Wiley

Specialty Allergy & Immunology

Date 2022 May 6

PMID 35518570

Authors

Wen Wang

Zheng-Yao Yu

Rong-Hua Song

Shuang-Tao He

Liang-Feng Shi

Jin-An Zhang

Affiliations

Soon will be listed here.

Abstract

Objective: To explore the association of gene polymorphisms with autoimmune thyroid diseases (AITDs) including Hashimoto's thyroiditis (HT) and Graves' illness (GD) as well as their clinical features.

Methods: rs6568431, rs548234, and rs6937876 were selected to investigate the correlation of single-nucleotide polymorphisms of gene with AITDs. Their frequencies in 824 AITD patients, including 271 HT patients and 553 GD patients, and 764 healthy controls were tested using both ligase detection reaction and multiplex polymerase chain reaction.

Results: Allele A frequency of rs6568431 in AITDs patients ( = 0.016, OR = 1.201, 95% CI = 1.034 - 1.394) and allele G frequency of rs6937876 in AITDs patients ( = 0.009, OR = 1.223, 95% CI = 1.052 - 1.422) and in GD patients ( = 0.009, OR = 1.247, 95% CI = 1.056 - 1.473) were significantly higher than those in the healthy controls. The frequency of G allele ( = 5.42E - 18, OR = 0.242, 95% CI = 0.173 - 0.339) of rs6937876 was significantly higher in GD patients with ophthalmopathy. However, no relationship was found between family history, age onset, and the three SNPs.

Conclusion: The study is the first to reveal the association between AITDs and polymorphisms, and gene is considered as a predisposing gene to AITDs, especially GDs.

Citing Articles

Autophagy in graves' ophthalmopathy.

Chen Y, Gao L, Liu Y, Shen Y, Diao J, Yang W Front Cell Dev Biol. 2023; 11:1158279.

PMID: 37123414 PMC: 10140433. DOI: 10.3389/fcell.2023.1158279.

References

Vanderpump M, Tunbridge W, French J, Appleton D, Bates D, Clark F . The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf). 1995; 43(1):55-68. DOI: 10.1111/j.1365-2265.1995.tb01894.x. View

Kang M, Kim M, Oh J, Kim Y, Song S, Kim S . Frameshift mutations of autophagy-related genes ATG2B, ATG5, ATG9B and ATG12 in gastric and colorectal cancers with microsatellite instability. J Pathol. 2009; 217(5):702-6. DOI: 10.1002/path.2509. View

Hui-Yuen J, Zhu L, Wong L, Jiang K, Chen Y, Liu T . Chromatin landscapes and genetic risk in systemic lupus. Arthritis Res Ther. 2016; 18(1):281. PMC: 5134118. DOI: 10.1186/s13075-016-1169-9. View

Raychaudhuri S, Thomson B, Remmers E, Eyre S, Hinks A, Guiducci C . Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk. Nat Genet. 2009; 41(12):1313-8. PMC: 3142887. DOI: 10.1038/ng.479. View

Gateva V, Sandling J, Hom G, Taylor K, Chung S, Sun X . A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nat Genet. 2009; 41(11):1228-33. PMC: 2925843. DOI: 10.1038/ng.468. View

Yang Z, Goronzy J, Weyand C . Autophagy in autoimmune disease. J Mol Med (Berl). 2015; 93(7):707-17. PMC: 4486076. DOI: 10.1007/s00109-015-1297-8. View

Nedjic J, Aichinger M, Emmerich J, Mizushima N, Klein L . Autophagy in thymic epithelium shapes the T-cell repertoire and is essential for tolerance. Nature. 2008; 455(7211):396-400. DOI: 10.1038/nature07208. View

Harley J, Alarcon-Riquelme M, Criswell L, Jacob C, Kimberly R, Moser K . Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet. 2008; 40(2):204-10. PMC: 3712260. DOI: 10.1038/ng.81. View

An C, Kim M, Yoo N, Park S, Lee S . Mutational and expressional analyses of ATG5, an autophagy-related gene, in gastrointestinal cancers. Pathol Res Pract. 2011; 207(7):433-7. DOI: 10.1016/j.prp.2011.05.002. View

10.

Huett A, Xavier R . Autophagy at the gut interface: mucosal responses to stress and the consequences for inflammatory bowel diseases. Inflamm Bowel Dis. 2009; 16(1):152-74. PMC: 3954538. DOI: 10.1002/ibd.20991. View

11.

Lu X, Zhou X, Guo J, Jia R, Zhao Y, Jiang Q . Rs548234 polymorphism at PRDM1-ATG5 region susceptible to rheumatoid arthritis in Caucasians is not associated with rheumatoid arthritis in Chinese Han population. Chin Med J (Engl). 2011; 124(18):2863-7. View

12.

Kim M, Song S, Lee J, Yoo N, Lee S . Expressional and mutational analyses of ATG5 gene in prostate cancers. APMIS. 2011; 119(11):802-7. DOI: 10.1111/j.1600-0463.2011.02812.x. View

13.

Lee H, Mattei L, Steinberg B, Alberts P, Lee Y, Chervonsky A . In vivo requirement for Atg5 in antigen presentation by dendritic cells. Immunity. 2010; 32(2):227-39. PMC: 2996467. DOI: 10.1016/j.immuni.2009.12.006. View

14.

Zhou X, Lu X, Lv J, Yang H, Qin L, Zhao M . Genetic association of PRDM1-ATG5 intergenic region and autophagy with systemic lupus erythematosus in a Chinese population. Ann Rheum Dis. 2011; 70(7):1330-7. DOI: 10.1136/ard.2010.140111. View

15.

Zhou X, Zhang H . Autophagy in immunity: implications in etiology of autoimmune/autoinflammatory diseases. Autophagy. 2012; 8(9):1286-99. PMC: 3442876. DOI: 10.4161/auto.21212. View

16.

Santeford A, Wiley L, Park S, Bamba S, Nakamura R, Gdoura A . Impaired autophagy in macrophages promotes inflammatory eye disease. Autophagy. 2016; 12(10):1876-1885. PMC: 5066937. DOI: 10.1080/15548627.2016.1207857. View

17.

Ye X, Zhou X, Zhang H . Exploring the Role of Autophagy-Related Gene 5 () Yields Important Insights Into Autophagy in Autoimmune/Autoinflammatory Diseases. Front Immunol. 2018; 9:2334. PMC: 6199349. DOI: 10.3389/fimmu.2018.02334. View

18.

Ravikumar B, Sarkar S, Davies J, Futter M, Garcia-Arencibia M, Green-Thompson Z . Regulation of mammalian autophagy in physiology and pathophysiology. Physiol Rev. 2010; 90(4):1383-435. DOI: 10.1152/physrev.00030.2009. View

19.

Huber A, Menconi F, Corathers S, Jacobson E, Tomer Y . Joint genetic susceptibility to type 1 diabetes and autoimmune thyroiditis: from epidemiology to mechanisms. Endocr Rev. 2008; 29(6):697-725. PMC: 2583387. DOI: 10.1210/er.2008-0015. View

20.

Dengjel J, Schoor O, Fischer R, Reich M, Kraus M, Muller M . Autophagy promotes MHC class II presentation of peptides from intracellular source proteins. Proc Natl Acad Sci U S A. 2005; 102(22):7922-7. PMC: 1142372. DOI: 10.1073/pnas.0501190102. View