Polymorphism in THBS1 gene is associated with post-refractive surgery chronic ocular surface inflammation.
Polymorphism in THBS1 gene is associated with post-refractive surgery chronic ocular surface inflammation.
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DOI：
10.1016/j.ophtha.2014.01.033
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发表时间：
2014-07
期刊：
影响因子：
13.7
通讯作者：
Masli S
中科院分区：
文献类型：
--
作者：
Contreras-Ruiz L;Ryan DS;Sia RK;Bower KS;Dartt DA;Masli S
确定血小板反应蛋白1（THBS 1）基因单核苷酸多态性（SNP）与屈光手术后慢性眼表炎症（角膜结膜炎）发生的相关性。回顾性队列研究。选择屈光手术的现役美国陆军士兵（n = 143）。使用Sequenom iPLEX Gold平台（Sequenom，San Diego，CA），使用手术前从参与者收集的结膜印迹细胞学样本收获DNA，用于对5种THBS 1 SNP（rs 1478604、rs 2228262、rs 2292305、rs 2228262和rs3743125）进行基因分型。手术后收集的样本用于收获RNA，通过实时聚合酶链反应（PCR）进行基因表达分析。参与者在手术后随访1年，以监测角膜结膜炎的状态。屈光手术后慢性角结膜炎发生的遗传学基础。携带3个SNPs的次要等位基因的人更容易患上慢性角结膜炎（rs 1478604：比值比[OR]，2.5; 95%置信区间[CI]，1.41-4.47; P = 2.5×10 - 3; rs 2228262和rs 2292305：OR，1.9; 95%CI，1.05-3.51; P = 4.8×10 - 2）。与纯合子主要等位基因对照组相比，rs 1478604次要等位基因携带者的眼表上皮细胞中血小板反应蛋白1（TSP 1）水平显著降低（P = 0.042），与角膜结膜炎相关的炎性细胞因子白细胞介素-1 β水平显著升高（P = 0.025）。THBS 1基因的遗传变异导致眼表上皮细胞中编码的糖蛋白TSP 1表达降低，这显著增加了屈光手术后发生慢性眼表炎症的易感性。需要在更大的样本量中进一步研究THBS 1 SNP。
To determine the association of single nucleotide polymorphisms (SNPs) of the thrombospondin 1 (THBS1) gene with development of chronic ocular surface inflammation (keratoconjunctivitis) after refractive surgery. Retrospective cohort study. Active duty U.S. Army soldiers (n = 143) who opted for refractive surgery. Conjunctival impression cytology samples collected from participants before the surgery were used to harvest DNA for genotyping 5 THBS1 SNPs (rs1478604, rs2228262, rs2292305, rs2228262, and rs3743125) using the Sequenom iPLEX Gold platform (Sequenom, San Diego, CA). Samples collected after surgery were used to harvest RNA for gene expression analysis by real-time polymerase chain reaction (PCR). Participants were followed for 1 year after surgery to monitor the status of keratoconjunctivitis. Genetic basis of the development of chronic keratoconjunctivitis after refractive surgery. Carriers of minor alleles of 3 SNPs each were found to be more susceptible to developing chronic keratoconjunctivitis (rs1478604: odds ratio [OR], 2.5; 95% confidence interval [CI], 1.41–4.47; P = 2.5×10−3; rs2228262 and rs2292305: OR, 1.9; 95% CI, 1.05–3.51; P = 4.8×10−2). Carriers of the rs1478604 minor allele expressed significantly reduced levels of thrombospondin 1 (TSP1) (P = 0.042) and increased levels of an inflammatory cytokine associated with keratoconjunctivitis, interleukin-1 β (P = 0.025), in their ocular surface epithelial cells compared with homozygous major allele controls. Genetic variation in the THBS1 gene that results in decreased expression of the encoded glycoprotein TSP1 in ocular surface epithelial cells significantly increases the susceptibility to develop chronic ocular surface inflammation after refractive surgery. Further investigation of THBS1 SNPs in a larger sample size is warranted.
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影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
影响因子：
2.8
作者：
Hovanesian, JA;Shah, SS;Maloney, RK
通讯作者：
Maloney, RK
影响因子：
4.8
作者：
Hannah, BLA;Misenheimer, TM;Mosher, DF
通讯作者：
Mosher, DF
影响因子：
3.6
作者：
Hiscott, P;Seitz, B;Naumann, GOH
通讯作者：
Naumann, GOH
影响因子：
56.9
作者：
Gabriel, SB;Schaffner, SF;Altshuler, D
通讯作者：
Altshuler, D