Additive effects of genetic variants associated with intraocular pressure in primary open-angle glaucoma.
Additive effects of genetic variants associated with intraocular pressure in primary open-angle glaucoma.
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原发性开角青光眼中与眼内压有关的遗传变异的添加剂。
DOI：
10.1371/journal.pone.0183709
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Japan Glaucoma Society Omics Group (JGS-OG)
中科院分区：
文献类型：
--
作者：
Mabuchi F;Mabuchi N;Sakurada Y;Yoneyama S;Kashiwagi K;Iijima H;Yamagata Z;Takamoto M;Aihara M;Iwata T;Kawase K;Shiga Y;Nishiguchi KM;Nakazawa T;Ozaki M;Araie M;Japan Glaucoma Society Omics Group (JGS-OG)
研究与眼内压（IOP）和IOP相关的遗传变异的累加效应、垂直杯盘比（VCDR）和作为原发性开角型青光眼（POAG）表型特征的高眼压性青光眼（HTG）或正常眼压性青光眼（NTG）之间的关联，并评价IOP相关遗传变异的累加效应预测IOP升高的临床有用性，对HTG（n = 255）和NTG（n = 261）日本患者和246例对照受试者的9种IOP相关遗传变异进行基因分型，这些遗传变异接近CAV 2、GAS 7、GLCCI 1/ICA 1、ABCA 1、ARHGEF 12、FAM 125 B、FNDC 3B、ABO和PTPRJ/AGBL 2。计算每例受试者这些遗传变异的风险等位基因总数作为遗传风险评分（GRS），并评估GRS与最大IOP、平均VCDR和POAG表型（HTG或NTG）之间的相关性。随着GRS的增加，最大IOP（P = 0.012）和VCDR（P = 0.010）显著增加。HTG组GRS（9.1±1.9）显著高于对照组（8.7±1.8）（P = 0.011）。以GRS≥12作为临界值的患者发生HTG（最大IOP≥ 22 mmHg）的风险是所有患者的2.54倍（P = 0.0085）。IOP相关的GRS方法证实了POAG中IOP相关遗传变异的累加效应使IOP和VCDR增加。HTG而非NTG患者的高IOP相关GRS表明HTG和NTG之间的遗传背景存在差异，并支持POAG患者的表型（HTG或NTG）取决于IOP相关遗传变异的累加效应的观点。上述IOP相关GRS的临界值可用于预测IOP升高的风险。
To investigate the association between the additive effects of genetic variants associated with intraocular pressure (IOP) and IOP, vertical cup-to-disc ratio (VCDR), and high tension glaucoma (HTG) or normal tension glaucoma (NTG) as phenotypic features of primary open-angle glaucoma (POAG), and to evaluate the clinical usefulness of the additive effects of IOP-related genetic variants for predicting IOP elevation, Japanese patients with HTG (n = 255) and NTG (n = 261) and 246 control subjects were genotyped for nine IOP-related genetic variants near CAV2, GAS7, GLCCI1/ICA1, ABCA1, ARHGEF12, FAM125B, FNDC3B, ABO, and PTPRJ/AGBL2. The total number of risk alleles of these genetic variants was calculated for each participant as a genetic risk score (GRS), and the association between the GRS and the maximum IOP, mean VCDR, and phenotype (HTG or NTG) of POAG was evaluated. As the GRS increased, the maximum IOP (P = 0.012) and VCDR (P = 0.010) significantly increased. The GRS (9.1±1.9) in patients with HTG was significantly higher (P = 0.011) than that (8.7±1.8) in control subjects. The patients with GRS≥12 as a cut-off value had a 2.54 times higher (P = 0.0085) risk on HTG (maximum IOP≥22mmHg) compared with all patients. The IOP-related GRS approach substantiated that the IOP and VCDR were increased by the additive effects of IOP-related genetic variants in POAG. The high IOP-related GRS in patients with HTG but not NTG shows that there are differences in the genetic background between HTG and NTG and supports the notion that the phenotype (HTG or NTG) in patients with POAG depends on the additive effects of IOP-related genetic variants. The above-mentioned cut-off value of IOP-related GRS may be clinically useful for predicting the risk of IOP elevation.
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影响因子：
4.5
作者：
Ramdas WD;van Koolwijk LM;Ikram MK;Jansonius NM;de Jong PT;Bergen AA;Isaacs A;Amin N;Aulchenko YS;Wolfs RC;Hofman A;Rivadeneira F;Oostra BA;Uitterlinden AG;Hysi P;Hammond CJ;Lemij HG;Vingerling JR;Klaver CC;van Duijn CM
通讯作者：
van Duijn CM
影响因子：
30.8
作者：
Gharahkhani, Puya;Burdon, Kathryn P.;Fogarty, Rhys;Sharma, Shiwani;Hewitt, Alex W.;Martin, Sarah;Law, Matthew H.;Cremin, Katie;Bailey, Jessica N. Cooke;Loomis, Stephanie J.;Pasquale, Louis R.;Haines, Jonathan L.;Hauser, Michael A.;Viswanathan, Ananth C.;McGuffin, Peter;Topouzis, Fotis;Foster, Paul J.;Graham, Stuart L.;Casson, Robert J.;Chehade, Mark;White, Andrew J.;Zhou, Tiger;Souzeau, Emmanuelle;Landers, John;Fitzgerald, Jude T.;Klebe, Sonja;Ruddle, Jonathan B.;Goldberg, Ivan;Healey, Paul R.;Mills, Richard A.;Wang, Jie Jin;Montgomery, Grant W.;Martin, Nicholas G.;Radford-Smith, Graham;Whiteman, David C.;Brown, Matthew A.;Wiggs, Janey L.;Mackey, David A.;Mitchell, Paul;MacGregor, Stuart;Craig, Jamie E.
通讯作者：
Craig, Jamie E.
影响因子：
13.7
作者：
Keltner, John L.;Johnson, Chris A.;Hypertension, Ocular
通讯作者：
Hypertension, Ocular
影响因子：
8.1
作者：
Kim, Na Rae;Park, Hyun Ju;Kim, Chan Yun
通讯作者：
Kim, Chan Yun
影响因子：
13.7
作者：
Lee, Mi Kyeong;Cho, Sung-Il;Sung, Joohon
通讯作者：
Sung, Joohon