ARMS2/HTRA1 locus can confer differential susceptibility to the advanced subtypes of age-related macular degeneration.
ARMS2/HTRA1 locus can confer differential susceptibility to the advanced subtypes of age-related macular degeneration.
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DOI：
10.1016/j.ajo.2010.08.015
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发表时间：
2011-02
影响因子：
4.2
通讯作者：
Seddon, Johanna M.
中科院分区：
文献类型：
--
作者：
Sobrin, Lucia;Reynolds, Robyn;Yu, Yi;Fagerness, Jesen;Leveziel, Nicolas;Bernstein, Paul S.;Souied, Eric H.;Daly, Mark J.;Seddon, Johanna M.
确定与年龄相关性黄斑变性（AMD）相关的遗传变异是否对脉络膜新生血管（CNV）和地理萎缩的风险有不同的影响。遗传关联研究。多中心研究。749名地理萎缩参与者和3209名CNV参与者来自塔夫茨医学中心、犹他大学年龄相关性眼病研究和Intercommunal de Creteil医院的4项AMD研究，采用类似的程序。根据眼底摄影和使用临床年龄相关性黄斑病变分期系统的检查来分配AMD等级。对所有样本进行基因分型，检测先前与AMD相关的单核苷酸多态性（snp）。在每个队列中使用PLINK比较CNV和地理萎缩参与者之间的等位基因频率，并进行Mantel-Haenszel meta分析以结合优势比（OR）。地理萎缩和CNV参与者之间等位基因频率的差异。CNV患者的ARMS2/HTRA1 rs10490924 T等位基因频率显著高于地理萎缩患者（OR为1.37；95%可信区间为1.21-1.54；P值= 4.2 × 10−7）。当排除单眼地理萎缩和对侧眼CNV的个体时，这一结果仍然具有统计学意义（P = 2.2 × 10−4）。包括CFH、C2/CFB、C3、CFI、LIPC和TIMP3在内的其他snp对CNV和地理萎缩的影响均无显著差异。在动力良好的样本中，ARMS2/HTRA1位点的遗传变异赋予CNV与地理萎缩的不同风险。
To determine if genetic variants that have been associated with age-related macular degeneration (AMD) have a differential effect on the risk of choroidal neovascularization (CNV) and geographic atrophy. Genetic association study. Multicenter study. Seven hundred forty-nine participants with geographic atrophy and 3209 participants with CNV were derived from 4 AMD studies with similar procedures from Tufts Medical Center, the Age-Related Eye Disease Study, University of Utah, and Hopital Intercommunal de Creteil. AMD grade was assigned based on fundus photography and examination using the clinical age-related maculopathy staging system. All samples were genotyped for single nucleotide polymorphisms (SNPs) previously associated with AMD. Allele frequencies were compared between participants with CNV and geographic atrophy using PLINK within each cohort and Mantel-Haenszel meta-analysis was performed to combine odds ratios (OR). Differences in allele frequencies between participants with geographic atrophy and CNV. The frequency of the T allele of ARMS2/HTRA1 rs10490924 was significantly higher in participants with CNV than in those with geographic atrophy (OR, 1.37; 95% confidence interval, 1.21–1.54; P value = 4.2 × 10−7). This result remained statistically significant when excluding individuals who had geographic atrophy in 1 eye and CNV in the contralateral eye (P = 2.2 × 10−4). None of the other SNPs showed a significant differential effect for CNV vs geographic atrophy, including CFH, C2/CFB, C3, CFI, LIPC, and TIMP3. Genetic variation at the ARMS2/HTRA1 locus confers a differential risk for CNV vs geographic atrophy in a well-powered sample.
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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：
30.8
作者：
Kathiresan S;Willer CJ;Peloso GM;Demissie S;Musunuru K;Schadt EE;Kaplan L;Bennett D;Li Y;Tanaka T;Voight BF;Bonnycastle LL;Jackson AU;Crawford G;Surti A;Guiducci C;Burtt NP;Parish S;Clarke R;Zelenika D;Kubalanza KA;Morken MA;Scott LJ;Stringham HM;Galan P;Swift AJ;Kuusisto J;Bergman RN;Sundvall J;Laakso M;Ferrucci L;Scheet P;Sanna S;Uda M;Yang Q;Lunetta KL;Dupuis J;de Bakker PI;O'Donnell CJ;Chambers JC;Kooner JS;Hercberg S;Meneton P;Lakatta EG;Scuteri A;Schlessinger D;Tuomilehto J;Collins FS;Groop L;Altshuler D;Collins R;Lathrop GM;Melander O;Salomaa V;Peltonen L;Orho-Melander M;Ordovas JM;Boehnke M;Abecasis GR;Mohlke KL;Cupples LA
通讯作者：
Cupples LA
影响因子：
4.4
作者：
Seddon JM;Reynolds R;Maller J;Fagerness JA;Daly MJ;Rosner B
通讯作者：
Rosner B
影响因子：
56.9
作者：
Edwards, AO;Ritter, R;Farrer, LA
通讯作者：
Farrer, LA