Skip to main content

Advertisement

SpringerLink
Log in

Genetic variations in autoimmune genes and VKH disease

  • Review
  • Published:
International Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

Vogt-Koyanagi-Harada (VKH) disease is a rare autoimmune disease. The autoimmune response in VKH disease is against the melanin-producing cells; therefore, in affected individuals melanocyte-containing organs manifest disease symptoms including eyes, ears, skin and nervous system. VKH is a multifactorial disease, and the precise cause of the VKH disease is unknown. Studies have suggested that both environmental and genetic factors are responsible for the VKH disease. In this review, the authors have collected all the available literature on the genetics of VKH to their knowledge and discussed the role of genetic variants in causing VKH disease.

Methods

An extensive literature search was performed in order to review all the published studies regarding VKH clinical phenotyping and genetic variants in VKH disease. Medline, PubMed, Cochrane library, and Scopus was searched using combination of keywords.

Results

It was found that variants in HLA genes, IL-12b, TNFSF4, and miR-20-5p genes are significantly associated with VKH; however, variants in genes ATG10, TNIP1 and CLEC16A did not achieve significant genome-wide association threshold. Moreover, polymorphisms in TNIP1 and CLEC16A play a protective role against VKH.

Conclusion

The authors conclude that increased sample size and a more homogeneous VKH patient population may reveal a significant association of variants in ATG10, TNIP1 and CLEC16A genes with VKH disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Herbort CP, Mochizuki M (2007) Vogt–Koyanagi–Harada disease: inquiry into the genesis of a disease name in the historical context of Switzerland and Japan. Int Ophthalmol 27(2–3):67–79

    PubMed  Google Scholar 

  2. Bismuth K, Arnheiter H (2009) Neural crest cell diversification and specification: melanocytes. Encycl Neurosci. https://doi.org/10.1016/B978-0-12-809324-5.02619-5

    Article  Google Scholar 

  3. Fang W, Yang P (2008) Vogt–Koyanagi–Harada. Curr Eye Res 33(7):517–523

    CAS  PubMed  Google Scholar 

  4. Walton RC (2014) Vogt–Koyanagi–Harada Disease. In: National Organization of Rare Disorders (NORD). February 12, 2014; Walton RC. Vogt–Koyanagi–Harada Disease. Medscape Reference, 2016

  5. Ondrey FG, Moldestad E, Mastroianni MA, Pikus A, Sklare D, Vernon E, Nusenblatt R, Smith J (2006) Sensorineural hearing loss in Vogt–Koyanagi–Harada syndrome. Laryngoscope 116(10):1873–1876

    PubMed  Google Scholar 

  6. Berker N, Ozdamar Y, Soykan E, Ozdal P, Ozkan SS (2007) Vogt–Koyanagi–Harada syndrome in children: report of a case and review of the literature. Ocul Immunol Inflamm 15(4):351–357

    PubMed  Google Scholar 

  7. Tabbara KF, Chavis PS, Freeman WR (1998) Vogt–Koyanagi–Harada syndrome in children compared to adults. Acta Ophthalmol Scand 76(6):723–726

    CAS  PubMed  Google Scholar 

  8. Yamaki K, Gocho K, Hayakawa K, Kondo I, Sakuragi S (2000) Tyrosinase family proteins are antigens specific to Vogt–Koyanagi–Harada disease. J Immunol 165(12):7323–7329

    CAS  PubMed  Google Scholar 

  9. Touitou V, Bodaghi B, Cassoux N, Tran TH, Rao NA, Cacoub P, LeHoang P (2005) Vogt–Koyanagi–Harada disease in patients with chronic hepatitis C. Am J Ophthalmol 140(5):949–952

    PubMed  Google Scholar 

  10. Levinson RD (2007) Immunogenetics of ocular inflammatory disease. Tissue Antigens 69(2):105–112

    CAS  PubMed  Google Scholar 

  11. Du L, Kijlstra A, Yang P (2009) Immune response genes in uveitis. Ocul Immunol Inflamm 17(4):249–256

    CAS  PubMed  Google Scholar 

  12. Zamecki KJ, Jabs DA (2010) HLA typing in uveitis: use and misuse. Am J Ophthalmol 149(2):189–193

    CAS  PubMed  Google Scholar 

  13. Itho S, Kurimoto S, Kouno T (1992) Vogt–Koyanagi–Harada disease in monozygotic twins. Int Ophthalmol 16:49–54

    CAS  PubMed  Google Scholar 

  14. Ishikawa A, Shiono T, Uchida S (1994) Vogt–Koyanagi–Harada disease in identical twins. Retina 14:435–437

    CAS  PubMed  Google Scholar 

  15. Rutzen AR, Ortega-Larrocea G, Frambach DA, Rao NA (1995) Macular edema in chronic Vogt–Koyanagi–Harada syndrome. Retina 15(6):475–479

    CAS  PubMed  Google Scholar 

  16. Mota LA, Santos AB (2010) Vogt–Koyanagi–Harada’s syndrome and its multisystem involvement. Rev Assoc Med Bras 56(5):590–595

    PubMed  Google Scholar 

  17. Caspi RR (2010) A look at autoimmunity and inflammation in the eye. J Clin Invest 120(9):3073–3083

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Weisz JM, Holland GN, Roer LN, Park MS, Yuge AJ, Moorthy RS, Forster DJ, Rao NA, Terasaki PI (1995) Association between Vogt–Koyanagi–Harada syndrome and HLA-DR1 and -DR4 in Hispanic patients living in southern California. Ophthalmology 102(7):1012–1015

    CAS  PubMed  Google Scholar 

  19. Caillat-Zucman S (2009) Molecular mechanisms of HLA association with autoimmune diseases. Tissue Antigens 73(1):1–8

    CAS  PubMed  Google Scholar 

  20. Davis JL, Mittal KK, Freidlin V, Mellow SR, Optican DC, Palestine AG, Nussenblatt RB (1990) HLA associations and ancestry in Vogt–Koyanagi–Harada disease and sympathetic ophthalmia. Ophthalmology 97(9):1137–1142

    CAS  PubMed  Google Scholar 

  21. Klein J, Sato A (2000) The HLA system. Second of two parts. N Engl J Med 343(11):782–786

    CAS  PubMed  Google Scholar 

  22. Marsh SG (2010) WHO Nomenclature Committee for Factors of the HLA System. Nomenclature for factors of the HLA system, update April 2010. Tissue Antigens 76(6):501–508

    CAS  PubMed  Google Scholar 

  23. Tagawa Y, Sugiura S, Yakura H, Wakisaka A, Aizawa M (1976) Letter: HLA and Vogt-Koyanagh-Harada syndrome. N Engl J Med 295(3):173

    CAS  PubMed  Google Scholar 

  24. Douglass SN, Douglass JM (1976) Letter: Hla and Vogt–Koyanagi–Harada syndrome. N Engl J Med 295(14):788

    CAS  PubMed  Google Scholar 

  25. Shindo Y, Ohno S, Yamamoto T, Nakamura S, Inoko H (1994) Complete association of the HLA-DRB1*04 and -DQB1*04 alleles with Vogt–Koyanagi–Harada’s disease. Hum Immunol 39(3):169–176

    CAS  PubMed  Google Scholar 

  26. Islam SM, Numaga J, Fujino Y, Hirata R, Matsuki K, Maeda H, Masuda K (1994) HLA class II genes in Vogt–Koyanagi–Harada disease. Invest Ophthalmol Vis Sci 35(11):3890–3896

    CAS  PubMed  Google Scholar 

  27. Damico FM, Bezerra FT, Silva GC, Gasparin F, Yamamoto JH (2009) New insights into Vogt–Koyanagi–Harada disease. Arq Bras Oftalmol 72(3):413–420

    PubMed  Google Scholar 

  28. Kim MH, Seong MC, Kwak NH, Yoo JS, Huh W, Kim TG, Han H (2000) Association of HLA with Vogt–Koyanagi–Harada syndrome in Koreans. Am J Ophthalmol 129(2):173–177

    CAS  PubMed  Google Scholar 

  29. Shi Y, Jia Y, Hou S, Fang J, Zhou Y, Kijlstra A, Yang P (2014) Association of a TNIP1 polymorphism with Vogt–Koyanagi–Harada syndrome but not with ocular Behcet’s disease in Han Chinese. PLoS ONE 9(5):e95573

    PubMed  PubMed Central  Google Scholar 

  30. Guergnon J, Combadière C (2012) Role of chemokines polymorphisms in diseases. Immunol Lett 145(1–2):15–22

    CAS  PubMed  Google Scholar 

  31. Charo IF, Ransohoff RM (2006) The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 354(6):610–621

    CAS  PubMed  Google Scholar 

  32. Yang P, Ye Z, Du L, Zhou Q, Qi J, Liang L, Wu L, Wang C, Kijlstra A (2018) Novel treatment regimen of Vogt–Koyanagi–Harada disease with a reduced dose of corticosteroids combined with immunosuppressive agents. Curr Eye Res 43(2):254–261

    CAS  PubMed  Google Scholar 

  33. Zhao M, Jiang Y, Abrahams IW (1991) Association of HLA antigens with Vogt–Koyanagi–Harada syndrome in a Han Chinese population. Arch Ophthalmol 109(3):368–370

    CAS  PubMed  Google Scholar 

  34. Shu Q, Yang P, Hou S, Li F, Chen Y, Du L, Jiang Z (2010) Interleukin-17 gene polymorphism is associated with Vogt–Koyanagi–Harada syndrome but not with Behçet’s disease in a Chinese Han population. Hum Immunol 71(10):988–991

    CAS  PubMed  Google Scholar 

  35. Hu K, Yang P, Jiang Z, Hou S, Du L, Li F (2010) STAT4 polymorphism in a Chinese Han population with Vogt–Koyanagi–Harada syndrome and Behçet’s disease. Hum Immunol 71(7):723–726

    CAS  PubMed  Google Scholar 

  36. Trinchieri G, Pflanz S, Kastelein RA (2003) The IL-12 family of heterodimeric cytokines: new players in the regulation of T cell responses. Immunity 19(5):641–644

    CAS  PubMed  Google Scholar 

  37. Trinchieri G (2003) Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 3(2):133–146

    CAS  PubMed  Google Scholar 

  38. Cleary AM, Tu W, Enright A, Giffon T, Dewaal-Malefyt R, Gutierrez K, Lewis DB (2003) Impaired accumulation and function of memory CD4 T cells in human IL-12 receptor beta 1 deficiency. J Immunol 170(1):597–603

    CAS  PubMed  Google Scholar 

  39. de Beaucoudrey L, Puel A, Filipe-Santos O, Cobat A, Ghandil P et al (2008) Mutations in STAT3 and IL12RB1 impair the development of human IL-17- producing T cells. J Exp Med 205:1543–1550

    PubMed  PubMed Central  Google Scholar 

  40. van de Vosse E, Haverkamp MH, Ramirez-Alejo N, Martinez-Gallo M, Blancas-Galicia L et al (2013) IL-12Rbeta1 deficiency: mutation update and description of the IL12RB1 variation database. Hum Mutat 34:1329–1339

    PubMed  PubMed Central  Google Scholar 

  41. Zhang GX, Yu S, Gran B, Li J, Siglienti I, Chen X, Calida D, Ventura E, Kamoun M, Rostami A (2003) Role of IL-12 receptor beta 1 in regulation of T cell response by APC in experimental autoimmune encephalomyelitis. J Immunol 171(9):4485–4492

    CAS  PubMed  Google Scholar 

  42. Fauconnier M, Palomo J, Bourigault ML, Meme S, Szeremeta F, Beloeil JC, Danneels A, Charron S, Rihet P, Ryffel B, Quesniaux VF (2012) IL-12Rβ2 is essential for the development of experimental cerebral malaria. J Immunol 188(4):1905–1914

    CAS  PubMed  Google Scholar 

  43. Szabo SJ, Dighe AS, Gubler U, Murphy KM (1997) Regulation of the interleukin (IL)-12R beta 2 subunit expression in developing T helper 1 (Th1) and Th2 cells. J Exp Med 185(5):817–824

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Toh ML, Kawashima M, Hot A, Miossec P, Miossec P (2010) Role of IL-17 in the Th1 systemic defects in rheumatoid arthritis through selective IL-12Rbeta2 inhibition. Ann Rheum Dis 69(8):1562–1567

    CAS  PubMed  Google Scholar 

  45. Li X, Bai L, Fang J, Hou S, Zhou Q, Yu H, Kijlstra A, Yang P (2014) Genetic variations of IL-12B, IL-12Rβ1, IL-12Rβ2 in Behcet’s disease and VKH syndrome. PLoS ONE 9(5):e98373

    PubMed  PubMed Central  Google Scholar 

  46. Wong RH, Wei JC, Huang CH, Lee HS, Chiou SY, Lin SH, Cai YW, Hung PH, Wang MF, Yang SF (2012) Association of IL-12B genetic polymorphism with the susceptibility and disease severity of ankylosing spondylitis. J Rheumatol 39(1):135–140

    CAS  PubMed  Google Scholar 

  47. Cargill EJ, Womack JE (2007) Detection of polymorphisms in bovine toll-like receptors 3, 7, 8, and 9. Genomics 89(6):745–755

    CAS  PubMed  Google Scholar 

  48. Bouyssou JM, Manier S, Huynh D, Issa S, Roccaro AM, Ghobrial IM (2014) Regulation of microRNAs in cancer metastasis. Biochim Biophys Acta 1845(2):255–265

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Wang Z, Chang C, Lu Q (2017) Epigenetics of CD4 + T cells in autoimmune diseases. Curr Opin Rheumatol 29(4):361–368

    CAS  PubMed  Google Scholar 

  50. Schaefer JS (2016) MicroRNAs: how many in inflammatory bowel disease? Curr Opin Gastroenterol 32(4):258–266

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Zhao S, Wang Y, Liang Y, Zhao M, Long H, Ding S, Yin H, Lu Q (2011) MicroRNA-126 regulates DNA methylation in CD4 + T cells and contributes to systemic lupus erythematosus by targeting DNA methyltransferase 1. Arthritis Rheum 63(5):1376–1386

    CAS  PubMed  Google Scholar 

  52. Yang G, Wu D, Zeng G, Jiang O, Yuan P, Huang S, Zhu J, Tian J, Weng Y, Rao Z (2015) Correlation between miR-126 expression and DNA hypomethylation of CD4 + T cells in rheumatoid arthritis patients. Int J Clin Exp Pathol 8(8):8929–8936

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Zhou Q, Hou S, Liang L, Li X, Tan X, Wei L, Lei B, Kijlstra A, Yang P (2014) MicroRNA-146a and Ets-1 gene polymorphisms in ocular Behcet’s disease and Vogt–Koyanagi–Harada syndrome. Ann Rheum Dis 73(1):170–176

    CAS  PubMed  Google Scholar 

  54. Hou S, Ye Z, Liao D, Bai L, Liu Y, Zhang J, Kijlstra A, Yang P (2016) miR-23a, miR-146a and miR-301a confer predisposition to Vogt–Koyanagi–Harada syndrome but not to Behcet’s disease. Sci Rep 6:20057

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Chang R, Yi S, Tan X, Huang Y, Wang Q, Su G, Zhou C, Cao Q, Yuan G, Kijlstra A, Yang P (2018) MicroRNA-20a-5p suppresses IL-17 production by targeting OSM and CCL1 in patients with Vogt–Koyanagi–Harada disease. Br J Ophthalmol 102(2):282–290

    PubMed  Google Scholar 

  56. Ehtesham N, Khorvash F, Kheirollahi M (2017) miR-145 and miR20a-5p potentially mediate pleiotropic effects of interferon-beta through mitogen-activated protein kinase signaling pathway in multiple sclerosis patients. J Mol Neurosci 61(1):16–24

    CAS  PubMed  Google Scholar 

  57. Roos RS, Loetscher M, Legler DF, Clark-Lewis I, Baggiolini M, Moser B (1997) Identification of CCR8, the receptor for the human CC chemokine I-309. J Biol Chem 272(28):17251–17254

    CAS  PubMed  Google Scholar 

  58. Gombert M, Dieu-Nosjean MC, Winterberg F, Bünemann E, Kubitza RC, Da Cunha L, Haahtela A, Lehtimäki S, Müller A, Rieker J, Meller S, Pivarcsi A, Koreck A, Fridman WH, Zentgraf HW, Pavenstädt H, Amara A, Caux C, Kemeny L, Alenius H, Lauerma A, Ruzicka T, Zlotnik A, Homey B (2005) CCL1-CCR8 interactions: an axis mediating the recruitment of T cells and Langerhans-type dendritic cells to sites of atopic skin inflammation. J Immunol 174(8):5082–5091

    CAS  PubMed  Google Scholar 

  59. Gonzalo JA, Qiu Y, Lora JM, Al-Garawi A, Villeval JL, Boyce JA, Martinez-A C, Marquez G, Goya I, Hamid Q, Fraser CC, Picarella D, Cote-Sierra J, Hodge MR, Gutierrez-Ramos JC, Kolbeck R, Coyle AJ (2007) Coordinated involvement of mast cells and T cells in allergic mucosal inflammation: critical role of the CC chemokine ligand 1:CCR8 axis. J Immunol 179(3):1740–1750

    CAS  PubMed  Google Scholar 

  60. Wagner S, Carpentier I, Rogov V, Kreike M, Ikeda F, Löhr F, Wu CJ, Ashwell JD, Dötsch V, Dikic I, Beyaert R (2008) Ubiquitin binding mediates the NF-kappaB inhibitory potential of ABIN proteins. Oncogene 27(26):3739–3745

    CAS  PubMed  Google Scholar 

  61. Nair RP, Duffin KC, Helms C, Ding J, Stuart PE, Goldgar D, Gudjonsson JE, Li Y, Tejasvi T, Feng BJ, Ruether A, Schreiber S, Weichenthal M, Gladman D, Rahman P, Schrodi SJ, Prahalad S, Guthery SL, Fischer J, Liao W, Kwok PY, Menter A, Lathrop GM, Wise CA, Begovich AB, Voorhees JJ, Elder JT, Krueger GG, Bowcock AM, Abecasis GR (2009) Collaborative association study of psoriasis. Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet 41(2):199–204

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Sun LD, Cheng H, Wang ZX, Zhang AP, Wang PG, Xu JH, Zhu QX, Zhou HS, Ellinghaus E, Zhang FR, Pu XM, Yang XQ, Zhang JZ, Xu AE, Wu RN, Xu LM, Peng L, Helms CA, Ren YQ, Zhang C, Zhang SM, Nair RP, Wang HY, Lin GS, Stuart PE, Fan X, Chen G, Tejasvi T, Li P, Zhu J, Li ZM, Ge HM, Weichenthal M, Ye WZ, Zhang C, Shen SK, Yang BQ, Sun YY, Li SS, Lin Y, Jiang JH, Li CT, Chen RX, Cheng J, Jiang X, Zhang P, Song WM, Tang J, Zhang HQ, Sun L, Cui J, Zhang LJ, Tang B, Huang F, Qin Q, Pei XP, Zhou AM, Shao LM, Liu JL, Zhang FY, Du WD, Franke A, Bowcock AM, Elder JT, Liu JJ, Yang S, Zhang XJ (2010) Association analyses identify six new psoriasis susceptibility loci in the Chinese population. Nat Genet 42(11):1005–1009

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Gateva V, Sandling JK, Hom G, Taylor KE, Chung SA, Sun X, Ortmann W, Kosoy R, Ferreira RC, Nordmark G, Gunnarsson I, Svenungsson E, Padyukov L, Sturfelt G, Jönsen A, Bengtsson AA, Rantapää-Dahlqvist S, Baechler EC, Brown EE, Alarcón GS, Edberg JC, Ramsey-Goldman R, McGwin G Jr, Reveille JD, Vilá LM, Kimberly RP, Manzi S, Petri MA, Lee A, Gregersen PK, Seldin MF, Rönnblom L, Criswell LA, Syvänen AC, Behrens TW, Graham RR (2009) A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nat Genet 41(11):1228–1233

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Bowes J, Orozco G, Flynn E, Ho P, Brier R, Marzo-Ortega H, Coates L, McManus R, Ryan AW, Kane D, Korendowych E, McHugh N, FitzGerald O, Packham J, Morgan AW, Bruce IN, Barton A (2011) Confirmation of TNIP1 and IL23A as susceptibility loci for psoriatic arthritis. Ann Rheum Dis 70(9):1641–1644

    PubMed  PubMed Central  Google Scholar 

  65. Allanore Y, Saad M, Dieudé P, Avouac J, Distler JH, Amouyel P, Matucci-Cerinic M, Riemekasten G, Airo P, Melchers I, Hachulla E, Cusi D, Wichmann HE, Wipff J, Lambert JC, Hunzelmann N, Tiev K, Caramaschi P, Diot E, Kowal-Bielecka O, Valentini G, Mouthon L, Czirják L, Damjanov N, Salvi E, Conti C, Müller M, Müller-Ladner U, Riccieri V, Ruiz B, Cracowski JL, Letenneur L, Dupuy AM, Meyer O, Kahan A, Munnich A, Boileau C, Martinez M (2011) Genome-wide scan identifies TNIP1, PSORS1C1, and RHOB as novel risk loci for systemic sclerosis. PLoS Genet 7(7):e1002091

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Zhang J, Chen Y, Shao Y, Wu Q, Guan M, Zhang W, Wan J, Yu B (2012) Identification of TNIP1 Polymorphisms by High Resolution Melting Analysis with Unlabelled Probe: Association with Systemic Lupus Erythematosus. Autoimmune Dis 2012:265823. https://doi.org/10.1155/2012/265823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Baranathan V, Stanford MR, Vaughan RW, Kondeatis E, Graham E, Fortune F, Madanat W, Kanawati C, Ghabra M, Murray PI, Wallace GR (2007) The association of the PTPN22 620 W polymorphism with Behcet’s disease. Ann Rheum Dis 66(11):1531–1533

    PubMed  PubMed Central  Google Scholar 

  68. Ramirez VP, Gurevich I, Aneskievich BJ (2012) Emerging roles for TNIP1 in regulating post-receptor signaling. Cytokine Growth Factor Rev 23(3):109–118

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Gurevich I, Zhang C, Francis N, Struzynsky CP, Livings SE, Aneskievich BJ (2013) Human TNFα-induced protein 3-interacting protein 1 (TNIP1) promoter activation is regulated by retinoic acid receptors. Gene 515(1):42–48

    CAS  PubMed  Google Scholar 

  70. International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN), Harley JB, Alarcón-Riquelme ME, Criswell LA, Jacob CO, Kimberly RP, Moser KL, Tsao BP, Vyse TJ, Langefeld CD, Nath SK, Guthridge JM, Cobb BL, Mirel DB, Marion MC, Williams AH, Divers J, Wang W, Frank SG, Namjou B, Gabriel SB, Lee AT, Gregersen PK, Behrens TW, Taylor KE, Fernando M, Zidovetzki R, Gaffney PM, Edberg JC, Rioux JD, Ojwang JO, James JA, Merrill JT, Gilkeson GS, Seldin MF, Yin H, Baechler EC, Li QZ, Wakeland EK, Bruner GR, Kaufman KM, Kelly JA (2008) Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet 40(2):204–210

    Google Scholar 

  71. Zhou J, Wu R, High AA, Slaughter CA, Finkelstein D, Rehg JE, Redecke V, Häcker H (2011) A20-binding inhibitor of NF-κB (ABIN1) controls Toll-like receptor-mediated CCAAT/enhancer-binding protein β activation and protects from inflammatory disease. Proc Natl Acad Sci USA 108(44):E998–E1006

    CAS  PubMed  Google Scholar 

  72. Clarke AJ, Ellinghaus U, Cortini A, Stranks A, Simon AK, Botto M, Vyse TJ (2015) Autophagy is activated in systemic lupus erythematosus and required for plasmablast development. Ann Rheum Dis 74(5):912–920

    PubMed  Google Scholar 

  73. Levine B, Mizushima N, Virgin HW (2011) Autophagy in immunity and inflammation. Nature 469(7330):323–335

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Alessandri CI, Barbati C, Vacirca D, Piscopo P, Confaloni A, Sanchez M, Maselli A, Colasanti T, Conti F, Truglia S, Perl A, Valesini G, Malorni W, Ortona E, Pierdominici M (2012) T lymphocytes from patients with systemic lupus erythematosus are resistant to induction of autophagy. FASEB J 26(11):4722–4732

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Gros F, Arnold J, Page N, Décossas M, Korganow AS, Martin T, Muller S (2012) Macroautophagy is deregulated in murine and human lupus T lymphocytes. Autophagy 8(7):1113–1123

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Bhattacharya S, Pal K, Sharma AK, Dutta SK, Lau JS, Yan IK, Wang E, Elkhanany A, Alkharfy KM, Sanyal A, Patel TC, Chari ST, Spaller MR, Mukhopadhyay D (2014) GAIP interacting protein C-terminus regulates autophagy and exosome biogenesis of pancreatic cancer through metabolic pathways. PLoS ONE 9(12):e114409

    PubMed  PubMed Central  Google Scholar 

  77. Kongara SI, Karantza V (2012) The interplay between autophagy and ROS in tumorigenesis. Front Oncol 2:171

    PubMed  PubMed Central  Google Scholar 

  78. Jo YK, Kim SC, Park IJ, Park SJ, Jin DH, Hong SW, Cho DH, Kim JC (2012) Increased expression of ATG10 in colorectal cancer is associated with lymphovascular invasion and lymph node metastasis. PLoS ONE 7(12):e52705

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Qin Z, Xue J, He Y, Ma H, Jin G, Chen J, Hu Z, Liu X, Shen H (2013) Potentially functional polymorphisms in ATG10 are associated with risk of breast cancer in a Chinese population. Gene 527(2):491–495

    CAS  PubMed  Google Scholar 

  80. Zheng M, Yu H, Zhang L, Li H, Liu Y, Kijlstra A, Yang P (2015) Association of ATG5 gene polymorphisms with Behçet’s disease and ATG10 gene polymorphisms With VKH syndrome in a Chinese Han population. Invest Ophthalmol Vis Sci 56(13):8280–8287

    CAS  PubMed  Google Scholar 

  81. Cambi A, Figdor CG (2005) Levels of complexity in pathogen recognition by C-type lectins. Curr Opin Immunol 17(4):345–351

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Berge T, Leikfoss IS, Harbo HF (2013) From identification to characterization of the multiple sclerosis susceptibility gene CLEC16A. Int J Mol Sci 14(3):4476–4497

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Zouk H, D’Hennezel E, Du X, Ounissi-Benkalha H, Piccirillo CA, Polychronakos C (2014) Functional evaluation of the role of C-type lectin domain family 16A at the chromosome 16p13 locus. Clin Exp Immunol 175(3):485–497

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Li K, Hou S, Qi J, Kijlstra A, Yang P (2015) A variant of CLEC16A gene confers protection for Vogt–Koyanagi–Harada syndrome but not for Behcet’s disease in a Chinese Han population. Exp Eye Res 132:225–230

    CAS  PubMed  Google Scholar 

  85. Latza U, Dürkop H, Schnittger S, Ringeling J, Eitelbach F, Hummel M, Fonatsch C, Stein H (1994) The human OX40 homolog: cDNA structure, expression and chromosomal assignment of the ACT35 antigen. Eur J Immunol 24(3):677–683

    CAS  PubMed  Google Scholar 

  86. Gramaglia I, Weinberg AD, Lemon M, Croft M (1998) Ox-40 ligand: a potent costimulatory molecule for sustaining primary CD4 T cell responses. J Immunol 161(12):6510–6517

    CAS  PubMed  Google Scholar 

  87. Xiao X, Kroemer A, Gao W, Ishii N, Demirci G, Li XC (2008) OX40/OX40L costimulation affects induction of Foxp3 + regulatory T cells in part by expanding memory T cells in vivo. J Immunol 181(5):3193–3201

    CAS  PubMed  Google Scholar 

  88. Lu S, Song S, Hou S, Li H, Yang P (2016) Association of TNFSF4 polymorphisms with Vogt–Koyanagi–Harada and Behcet’s Disease in Han Chinese. Sci Rep. 6:37257

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Yue Y, Zhang J, Yang L, Liu S, Qi J, Cao Q, Zhou C, Wang Y, Kijlstra A, Yang P, Hou S (2018) Association of long noncoding RNAs polymorphisms with ankylosing spondylitis, Vogt–Koyanagi–Harada Disease, and Behcet’s Disease. Invest Ophthalmol Vis Sci 59(2):1158–1166

    CAS  PubMed  Google Scholar 

  90. Peng Z, Jiang S, Wu M, Zhou X, Wang Q (2017) Expression and role of interleukin-9 in Vogt–Koyanagi–Harada disease. Mol Vis 23:538–547

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Zhu Y, Yu H, Qiu Y, Ye Z, Su W, Deng J, Cao Q, Yuan G, Kijlstra A, Yang P (2017) Promoter hypermethylation of GATA3, IL-4, and TGF-β confers susceptibility to Vogt–Koyanagi–Harada Disease in Han Chinese. Invest Ophthalmol Vis Sci 58(3):1529–1536

    CAS  PubMed  Google Scholar 

  92. Luster AD (1998) Chemokines–chemotactic cytokines that mediate inflammation. N Engl J Med 338(7):436–445

    CAS  PubMed  Google Scholar 

  93. Huang Y, Yu H, Cao Q, Deng J, Huang X, Kijlstra A, Yang P (2017) The Association of Chemokine Gene Polymorphisms with VKH and Behcet’s Disease in a Chinese Han Population. Biomed Res Int 2017:1274960

    PubMed  PubMed Central  Google Scholar 

  94. Al-Barry MA, Albalawi AM, Sayf MA, Badawi A, Afzal S, Latif M, Samman MI, Basit S (2016) Sequence analysis of four vitamin D family genes (VDR, CYP24A1, CYP27B1 and CYP2R1) in Vogt–Koyanagi–Harada (VKH) patients: identification of a potentially pathogenic variant in CYP2R1. BMC Ophthalmol 16(1):172

    PubMed  PubMed Central  Google Scholar 

  95. Yi X, Yang P, Sun M, Yang Y, Li F (2011) Decreased 1,25-Dihydroxyvitamin D3 level is involved in the pathogenesis of Vogt–Koyanagi–Harada (VKH) disease. Mol Vis 17:673–679

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Schutyser E, Struyf S, Van Damme J (2003) The CC chemokine CCL20 and its receptor CCR6. Cytokine Growth Factor Rev 14:409–426

    CAS  PubMed  Google Scholar 

  97. Liu B, Deng T, Zhu L, Zhong J (2018) Association of human leukocyte antigen (HLA)-DQ and HLA-DQA1/DQB1 alleles with Vogt–Koyanagi–Harada disease: a systematic review and meta-analysis. Medicine (Baltimore) 97:e9914

    CAS  Google Scholar 

  98. Sheereen A, Gaafar A, Iqneibi A, Eldali A, Tabbara KF, Adra C, Al-Hussein K (2011) A study of KIR genes and HLA-C in Vogt–Koyanagi–Harada disease in Saudi Arabia. Mol Vis 17:3523–3528

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Qi J, Du L, Deng J et al (2019) Replication of Genome-Wide Association Analysis Identifies New Susceptibility Loci at Long Noncoding RNA Regions for Vogt–Koyanagi–Harada Disease. Invest Ophthalmol Vis Sci 60:4820–4829

    CAS  PubMed  Google Scholar 

  100. Zhang Q, Qi J, Hou S et al (2014) A functional variant of PTPN22 confers risk for Vogt–Koyanagi–Harada syndrome but not for ankylosing spondylitis. PLoS ONE 9:e96943

    PubMed  PubMed Central  Google Scholar 

  101. Yue Y, Zhang J, Yang L, Liu S, Qi J, Cao Q, Zhou C, Wang Y, Kijlstra A, Yang P, Hou S (2018) Association of long noncoding RNAs polymorphisms with Ankylosing Spondylitis, Vogt–Koyanagi–Harada Disease, and Behcet’s disease. Invest Ophthalmol Vis Sci 59:1158–1166

    CAS  PubMed  Google Scholar 

  102. Xu L, Zhao T, Yuan G, Hou S, Zeng W, Chen F (2019) PRKCQ rs4750316 is associated with Vogt–Koyanagi–Harada syndrome in a Han Chinese population. Mol Vis 25:834–842

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Zhang C, Liu S, Hou S, Lei B, Zheng X, Xiao X, Kijlstra A, Yang P (2013) MIF gene polymorphisms confer susceptibility to Vogt–Koyanagi–Harada syndrome in a Han Chinese population. Invest Ophthalmol Vis Sci 54:7734–7738

    CAS  PubMed  Google Scholar 

  104. Hu K, Hou S, Li F, Xiang Q, Kijlstra A, Yang P (2013) JAK1, but not JAK2 and STAT3, confers susceptibility to Vogt–Koyanagi–Harada (VKH) syndrome in a Han Chinese population. Invest Ophthalmol Vis Sci 54:3360–3365

    CAS  PubMed  Google Scholar 

  105. Yi X, Du L, Hou S et al (2013) FGFR1OP tagSNP but not CCR6 polymorphisms are associated with Vogt–Koyanagi–Harada syndrome in Chinese Han. PLoS ONE 8:e69358

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Hou S, Du L, Lei B et al (2014) Genome-wide association analysis of Vogt–Koyanagi–Harada syndrome identifies two new susceptibility loci at 1p31.2 and 10q21.3. Nat Genet 46:1007–1011

    CAS  PubMed  Google Scholar 

  107. Shi T, Lv W, Zhang L, Chen J, Chen H (2014) Association of HLA-DR4/HLA-DRB1*04 with Vogt–Koyanagi–Harada disease: a systematic review and meta-analysis. Sci Rep 4:6887

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Authors acknowledge the participation and contribution of all patients.

Funding

No funds were obtained to perform this study.

Author information

Authors and Affiliations

  1. Department of Biology, College of Science, King AbdulAziz University Jeddah, Jeddah, Saudi Arabia

    Alia M. Albalawi

  2. Center for Genetics and Inherited Diseases, Taibah University Almadinah Almunawwarah, Medina, Saudi Arabia

    Alia M. Albalawi

  3. Department of Ophthalmology, College of Medicine, Taibah University Almadinah Almunawwarah, Medina, Saudi Arabia

    Maan A. Al-Barry

Authors
  1. Alia M. Albalawi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maan A. Al-Barry
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MAA conceived the idea and provided data and images of patients, and AMA drafted the manuscript. Both authors have seen and agreed on the final draft.

Corresponding author

Correspondence to Maan A. Al-Barry.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest.

Ethics approval and consent to participate

Approval to conduct the study was obtained from the research ethics committee of Taibah University Almadinah. All patients signed informed consents for participation in this study.

Consent for publication

All patients given informed consents for publications of their images and data.

Availability of data and material

All the data is available on request.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Albalawi, A.M., Al-Barry, M.A. Genetic variations in autoimmune genes and VKH disease. Int Ophthalmol 40, 3175–3186 (2020). https://doi.org/10.1007/s10792-020-01407-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10792-020-01407-3

Keywords

Search

Navigation