Phenotypic Characterization of Complement Factor H R1210C Rare Genetic Variant in Age-Related Macular Degeneration.
Phenotypic Characterization of Complement Factor H R1210C Rare Genetic Variant in Age-Related Macular Degeneration.
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DOI：
10.1001/jamaophthalmol.2015.0814
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发表时间：
2015-07
影响因子：
8.1
通讯作者：
Seddon JM
中科院分区：
文献类型：
--
作者：
Ferrara D;Seddon JM
补体因子HR 1210 C罕见变异体赋予年龄相关性黄斑变性最强的遗传风险和较早的发病年龄;然而，其相关表型尚未得到很好的表征。描述R1210 C罕见变异白色人群的特定眼底特征。通过对每例患者的所有可用眼底图像进行系统回顾，包括彩色摄影、荧光素血管造影、眼底自发荧光和光学相干断层扫描，在三级眼科转诊中心回顾性分析诊断和疾病分期的特异性眼底特征。在2012年至2014年进行的这项回顾性观察性研究中，从视网膜相关黄斑变性研究中确定了入组的变异患者及其无变异的家庭成员，作为基于家庭的研究组。对于有变异但无家庭成员入组研究的患者，从数据库中随机选择年龄匹配的无变异的对照个体。评估黄斑玻璃疣的存在（黄斑玻璃疣评分）和估计数量（黄斑玻璃疣总评分）。还评估了黄斑外区域玻璃疣的存在（黄斑外玻璃疣评分）、色素异常和疾病分期。二元逻辑回归模型用于评估罕见变异状态与眼部表型之间的关联。共分析了143例患者（283只眼）的图像，其中包括62例罕见变异患者。玻璃疣评分协变量与R1210 C罕见变异相关。与未携带变异体的患者相比，携带变异体的患者中黄斑玻璃疣评分和总黄斑玻璃疣评分水平最高的比例更大（分别为57.9% vs 16.7%和52.9% vs 14.2%;两种评分的趋势P <0.001）。携带这种罕见变异的患者患晚期疾病的可能性要大得多（比值比，7.0; 95%CI，3.1-16.2; P <0.001）。在携带变异的患者中观察到地图状萎缩的发生率更高（比值比，13.7; 95%CI，5.0-37.7; P <0.001）。补体因子HR 1210 C罕见变体的典型表型与黄斑和整个眼底中广泛的玻璃疣积累相关，以及与患有晚期疾病的高风险相关。更好地描述年龄相关性黄斑变性的遗传特征可能对这种威胁视力的疾病的筛查和未来的治疗策略很重要。
The complement factor H R1210C rare variant confers the strongest genetic risk for age-related macular degeneration and earlier age at onset; however, its associated phenotype has not been well characterized. To describe specific fundus features of a white population with the R1210C rare variant. Fundus features specific for diagnosis and disease staging were retrospectively characterized by systematic review of all available fundus images for each patient, including color photography, fluorescein angiography, fundus autofluorescence, and optical coherence tomography, at a tertiary ophthalmologic referral center. For this retrospective observational study conducted from 2012 to 2014, enrolled patients with the variant and their family members without the variant were identified from the Age-Related Macular Degeneration Study for a family-based study arm. For patients with the variant but without a family member enrolled in the study, age-matched comparison individuals without the variant were selected randomly from the database. The presence of drusen in the macula (macular drusen score) and estimated number (total macular drusen score) were assessed. The presence of drusen in the extramacular regions (extramacular drusen score), pigmentary abnormalities, and disease staging were also evaluated. Binary logistic regression models were used to evaluate the association between rare variant status and ocular phenotypes. Images from a total of 143 patients (283 eyes), including 62 patients with the rare variant, were analyzed. Drusen score covariates were associated with the R1210C rare variant. A larger proportion of patients carrying the variant had the highest level of macular and total macular drusen scores compared with those without the variant (57.9% vs 16.7% and 52.9% vs 14.2%, respectively; P for trend < .001 for both scores). Patients carrying the rare variant had a much greater likelihood of having advanced disease (odds ratio, 7.0; 95% CI, 3.1-16.2; P < .001). A higher prevalence of geographic atrophy was observed among patients carrying the variant (odds ratio, 13.7; 95% CI, 5.0-37.7; P < .001). The typical phenotype of the complement factor H R1210C rare variant is associated with extensive drusen accumulation in the macula and throughout the fundus, as well as with a high risk for having advanced disease. Better characterization of genetic profiles in age-related macular degeneration may be important for screening and future therapeutic strategies for this vision-threatening condition.
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DOI：
10.4049/jimmunol.0804031
发表时间：
2009-06-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ferreira VP;Herbert AP;Cortés C;McKee KA;Blaum BS;Esswein ST;Uhrín D;Barlow PN;Pangburn MK;Kavanagh D
通讯作者：
Kavanagh D
DOI：
10.1073/pnas.0501536102
发表时间：
2005-05-17
影响因子：
11.1
作者：
Hageman, GS;Anderson, DH;Allikmets, R
通讯作者：
Allikmets, R
影响因子：
5.2
作者：
Fagerness, Jesen A.;Maller, Julian B.;Seddon, Johanna M.
通讯作者：
Seddon, Johanna M.
影响因子：
17.8
作者：
Boon, Camiel J. F.;van de Ven, Johannes P. H.;Klevering, B. Jeroen
通讯作者：
Klevering, B. Jeroen
影响因子：
30.8
作者：
Fritsche, Lars G.;Chen, Wei;Schu, Matthew;Yaspan, Brian L.;Yu, Yi;Thorleifsson, Gudmar;Zack, Donald J.;Arakawa, Satoshi;Cipriani, Valentina;Ripke, Stephan;Igo, Robert P., Jr.;Buitendijk, Gabrielle H. S.;Sim, Xueling;Weeks, Daniel E.;Guymer, Robyn H.;Merriam, Joanna E.;Francis, Peter J.;Hannum, Gregory;Agarwal, Anita;Armbrecht, Ana Maria;Audo, Isabelle;Aung, Tin;Barile, Gaetano R.;Benchaboune, Mustapha;Bird, Alan C.;Bishop, Paul N.;Branham, Kari E.;Brooks, Matthew;Brucker, Alexander J.;Cade, William H.;Cain, Melinda S.;Campochiaroll, Peter A.;Chan, Chi-Chao;Cheng, Ching-Yu;Chew, Emily Y.;Chin, Kimberly A.;Chowers, Itay;Clayton, David G.;Cojocaru, Radu;Conley, Yvette P.;Cornes, Belinda K.;Daly, Mark J.;Dhillon, Baljean;Edwards, Albert;Evangelou, Evangelos;Fagemess, Jesen;Ferreyra, Henry A.;Friedman, James S.;Geirsdottir, Asbjorg;George, Ronnie J.;Gieger, Christian;Gupta, Neel;Hagstrom, Stephanie A.;Harding, Simon P.;Haritoglou, Christos;Heckenlively, John R.;Hoz, Frank G.;Hughes, Guy;Ioannidis, John P. A.;Ishibashi, Tatsuro;Joseph, Peronne;Jun, Gyungah;Kamatani, Yoichiro;Katsanis, Nicholas;Keilhauer, Claudia N.;Khan, Jane C.;Kim, Ivana K.;Kiyohara, Yutaka;Klein, Barbara E. K.;Klein, Ronald;Kovach, Jaclyn L.;Kozak, Igor;Lee, Clara J.;Lee, Kristine E.;Lichtner, Peter;Lotery, Andrew J.;Meitinger, Thomas;Mitchell, Paul;Mohand-Saied, Saddek;Moore, Anthony T.;Morgan, Denise J.;Morrison, Margaux A.;Myers, Chelsea E.;Naj, Adam C.;Nakamura, Yusuke;Okada, Yukinori;Orlin, Anton;Ortube, M. Carolina;Othman, Mohammad I.;Pappas, Chris;Park, Kyu Hyung;Pauer, Gayle J. T.;Peachey, Neal S.;Poch, Olivier;Priya, Rinki Ratna;Reynolds, Robyn;Richardson, Andrea J.;Ripp, Raymond;Rudolph, Guenther;Ryu, Euijung;Sahel, Jose-Alain;Schaumberg, Debra A.;Scholl, Hendrik P. N.;Schwartz, Stephen G.;Scott, William K.;Shahid, Humma;Sigurdsson, Haraldur;Silvestri, Giuliana;Sivakumaran, Theru A.;Smith, R. Theodore;Sobrin, Lucia;Souied, Eric H.;Stambolian, Dwight E.;Stefansson, Hreinn;Sturgill-Short, Gwen M.;Takahashi, Atsushi;Tosakulwong, Nirubol;Truitt, Barbara J.;Tsironi, Evangelia E.;Uitterlinden, Andre G.;van Duijn, Cornelia M.;Vijaya, Lingam;Vingerling, Johannes R.;Vithana, Eranga N.;Webster, Andrew R.;Wichmann, H-Erich;Winkler, Thomas W.;Wong, Tien Y.;Wright, Alan F.;Zelenika, Diana;Zhang, Ming;Zhao, Ling;Zhang, Kang;Klein, Michael L.;Hageman, Gregory S.;Lathrop, G. Mark;Stefansson, Kari;Allikmets, Rando;Baird, Paul N.;Gorin, Michael B.;Wang, Jie Jin;Klaver, Caroline C. W.;Seddon, Johanna M.;Pericak-Vance, Margaret A.;Iyengar, Sudha K.;Yates, John R. W.;Swaroop, Anand;Weber, Bernhard H. F.;Kubo, Michiaki;DeAngelis, Margaret M.;Leveillard, Thierry;Thorsteinsdottir, Unnur;Haines, Jonathan L.;Farrer, Lindsay A.;Heid, Iris M.;Abecasis, Goncalo R.
通讯作者：
Abecasis, Goncalo R.