title: miR-23a, miR-146a and miR-301a confer predisposition to Vogt-Koyanagi-Harada syndrome but not to Behcet's disease.
abstract: Ninety-eight miRNAs are involved in the immune response. However, the genetic roles of these miRNAs remain unclear in Behcet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome. This study aimed to explore the association and functional roles of copy number variants (CNV) in several miRNAs with BD and VKH syndrome. Genotyping of CNVs was examined by TaqMan PCR. The expression of miR-23a, transfection efficiency and cytokine production were measured by real-time PCR, flow cytometry or ELISA. First, replication and combined studies for miR-23a, miR-146a and miR-301a demonstrated a similar association with VKH syndrome (Combined: P = 5.53 × 10(-8); P = 8.43 × 10(-31); P = 9.23 × 10(-8), respectively). No association of CNVs of the above mentioned miRNAs was observed in BD patients. mRNA expression of miR-23a showed a positive association with its copy numbers. Additionally, individuals with high copy number of miR-23a show an increased production of interleukin-6 (IL-6), but not IL-8 and monocyte chemoattractant protein-1 (MCP-1) by stimulated PBMCs. miR-23a transfected ARPE-19 cells modulated the production of IL-6 and IL-8, but not MCP-1. Our results suggest that CNVs of miR-146a, miR-23a and miR-301a confer susceptibility to VKH syndrome, but not to BD. The contribution of miR-23a to VKH syndrome may be mediated by increasing the production of IL-6.
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Eye Institute and Chongqing Key Laboratory of Ophthalmology, Chongqing, China.
authors.forename: Shengping
authors.initials: S
authors.lastname: Hou
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Eye Institute and Chongqing Key Laboratory of Ophthalmology, Chongqing, China.
authors.forename: Zi
authors.initials: Z
authors.lastname: Ye
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Eye Institute and Chongqing Key Laboratory of Ophthalmology, Chongqing, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liao
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Eye Institute and Chongqing Key Laboratory of Ophthalmology, Chongqing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Bai
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Eye Institute and Chongqing Key Laboratory of Ophthalmology, Chongqing, China.
authors.forename: Yunjia
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Eye Institute and Chongqing Key Laboratory of Ophthalmology, Chongqing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: University Eye Clinic Maastricht, Maastricht, The Netherlands.
authors.forename: Aize
authors.initials: A
authors.lastname: Kijlstra
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.|Chongqing Eye Institute and Chongqing Key Laboratory of Ophthalmology, Chongqing, China.
authors.forename: Peizeng
authors.initials: P
authors.lastname: Yang
mesh_terms: D000328:Adult; D001528:Behcet Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D056915:DNA Copy Number Variations; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D018628:Gene Dosage; D015870:Gene Expression; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D055213:Retinal Pigment Epithelium / Q000378:metabolism; D014607:Uveomeningoencephalitic Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D016207:Cytokines; C542542:MIRN146 microRNA, human; C552430:MIRN23a microRNA, human; C550735:MIRN301A microRNA, human; D035683:MicroRNAs
references.citation: Invest Ophthalmol Vis Sci. 2012 Jun;53(7):3827-33
references.pmid: 22589430
references.citation: Lancet. 1990 May 5;335(8697):1078-80
references.pmid: 1970380
references.citation: Arthritis Rheumatol. 2014 Jan;66(1):49-59
references.pmid: 24449575
references.citation: Arthritis Rheum. 2009 Apr;60(4):1065-75
references.pmid: 19333922
references.citation: Clin Med Res. 2006 Dec;4(4):294-309
references.pmid: 17210978
references.citation: Rheumatology (Oxford). 2009 Apr;48(4):347-54
references.pmid: 19164426
references.citation: Int J Mol Sci. 2013 Feb 25;14(3):4375-84
references.pmid: 23439547
references.citation: J Cell Biochem. 2013 Sep;114(9):2160-9
references.pmid: 23553990
references.citation: PLoS Genet. 2011 Jun;7(6):e1002128
references.pmid: 21738483
references.citation: Ann Rheum Dis. 2001 Nov;60(11):996-1002
references.pmid: 11602462
references.citation: Am J Ophthalmol. 2001 May;131(5):647-52
references.pmid: 11336942
references.citation: Invest Ophthalmol Vis Sci. 2012 Aug;53(9):5665-74
references.pmid: 22815348
references.citation: Ophthalmology. 2007 Mar;114(3):606-14
references.pmid: 17123618
references.citation: Ophthalmology. 2015 Mar;122(3):518-23
references.pmid: 25439430
references.citation: Rheumatol Int. 2014 Oct;34(10):1395-400
references.pmid: 24719227
references.citation: J Leukoc Biol. 2014 Oct;96(4):633-45
references.pmid: 25030422
references.citation: Tissue Antigens. 1999 Sep;54(3):213-20
references.pmid: 10519357
references.citation: Hum Genet. 2013 Dec;132(12):1395-404
references.pmid: 23928854
references.citation: Proc Natl Acad Sci U S A. 2012 May 15;109(20):E1248-57
references.pmid: 22517757
references.citation: Jpn J Ophthalmol. 2007 Jan-Feb;51(1):41-4
references.pmid: 17295139
references.citation: PLoS One. 2013;8(10):e77249
references.pmid: 24143215
references.citation: Inflammation. 2015 Oct;38(5):1787-93
references.pmid: 25832477
references.citation: Ophthalmology. 2008 Feb;115(2):312-318.e4
references.pmid: 17692378
references.citation: Arthritis Rheum. 2012 Dec;64(12):4104-13
references.pmid: 23001997
references.citation: Eur J Immunol. 2012 Aug;42(8):2100-8
references.pmid: 22585398
references.citation: J Immunol. 2000 Dec 15;165(12):7323-9
references.pmid: 11120868
references.citation: Rheumatology (Oxford). 2006 Dec;45(12):1461-5
references.pmid: 16998234
references.citation: Autoimmun Rev. 2013 Oct;12(12):1160-5
references.pmid: 23860189
references.citation: Mult Scler. 2013 Dec;19(14):1938-42
references.pmid: 24277735
references.citation: Eur J Immunol. 2013 Oct;43(10):2771-82
references.pmid: 23780851
references.citation: Clin Immunol. 2008 Oct;129(1):170-5
references.pmid: 18657476
references.citation: Br J Ophthalmol. 2014 Dec;98(12):1733-7
references.pmid: 25185257
references.citation: Nat Genet. 2014 Sep;46(9):1007-11
references.pmid: 25108386
references.citation: Curr Eye Res. 2005 Nov;30(11):943-8
references.pmid: 16282128
references.citation: Am J Ophthalmol. 2014 Feb;157(2):488-494.e6
references.pmid: 24184224
references.citation: Curr Drug Targets Inflamm Allergy. 2005 Feb;4(1):81-3
references.pmid: 15720240
references.citation: Nat Genet. 2013 Mar;45(3):319-24
references.pmid: 23396137
references.citation: Gene. 2013 Jun 1;521(2):259-64
references.pmid: 23545308
references.citation: Iran J Immunol. 2013 Jun;10(2):103-9
references.pmid: 23811549
references.citation: Cell. 2004 Jan 23;116(2):281-97
references.pmid: 14744438
references.citation: Ophthalmology. 2014 Jan;121(1):365-76
references.pmid: 24169255
references.citation: Ann Rheum Dis. 2014 Jan;73(1):170-6
references.pmid: 23268366
references.citation: Nat Genet. 2013 Feb;45(2):202-7
references.pmid: 23291587
references.citation: Exp Hematol. 2010 Aug;38(8):629-640.e1
references.pmid: 20399246
references.citation: Arthritis Rheum. 2013 Nov;65(11):2963-70
references.pmid: 23918728
references.citation: Curr Opin Rheumatol. 2014 Jan;26(1):56-63
references.pmid: 24257369
references.citation: Int Forum Allergy Rhinol. 2013 Aug;3(8):612-20
references.pmid: 23704072
references.citation: Autoimmun Rev. 2012 Jul;11(9):636-41
references.pmid: 22100329
references.citation: Nat Genet. 2010 Aug;42(8):698-702
references.pmid: 20622878
references.citation: Ocul Immunol Inflamm. 2002 Dec;10(4):263-79
references.pmid: 12854035
references.citation: J Cell Mol Med. 2014 Nov;18(11):2225-34
references.pmid: 25209759
references.citation: Lupus. 2014 Sep;23(10):1023-30
references.pmid: 24803388
references.citation: Clin Exp Rheumatol. 2011 Jul-Aug;29(4 Suppl 67):S3-5
references.pmid: 21968232
references.citation: Clin Endocrinol (Oxf). 2014 Aug;81(2):276-81
references.pmid: 24533739
references.citation: Hum Mol Genet. 2009 Apr 15;18(R1):R1-8
references.pmid: 19297395
references.citation: Invest Ophthalmol Vis Sci. 2006 Jun;47(6):2547-54
references.pmid: 16723469
references.citation: Ann Rheum Dis. 1998 Jan;57(1):45-8
references.pmid: 9536823