Institute of Applied Ophthalmolbiology (IOBA-Eye Institute), University of Valladolid, Spain.
Invest Ophthalmol Vis Sci. 2013 Mar 5;54(3):1665-78. doi: 10.1167/iovs.12-10931.
Proliferative vitreoretinopathy (PVR) is still the major cause of failure of retinal detachment (RD) surgery and although the risk for developing this complication is associated with some clinical characteristics, the correlation is far from absolute, raising the possibility of genetic susceptibility. The objective of this study was to analyze the genetic contribution to PVR in patients undergoing RD surgery, the Retina 4 Project.
A candidate gene association study was conducted in 2006 in a Spanish population of 450 patients suffering from primary rhegmatogenous RD. Replication was carried out in a larger population undergoing RD surgery at several European centers among 546 new patients. Single nucleotide polymorphism (SNP) of 30 genes known to be involved with inflammation were analyzed. For replication stage, those genes previously detected as significantly associated with PVR were genotyped. Distribution of allelic and haplotypic frequencies in case and control group were analyzed. Single and haplotypic analysis were assessed. The Rosenberg two-stage method was used to correct for single and multiple analyses.
After correction for multiple comparisons, four genes were significantly associated with PVR: SMAD7 (P = 0.004), PIK3CG (P = 0.009), TNF locus (P = 0.0005), and TNFR2 (P = 0.019) In the European sample, replication was observed in SMAD7 (P = 0.047) and the TNF locus (P = 0.044).
These results confirm the genetic contribution to PVR and the implication of SMAD7 and TNF locus in the development of PVR. This finding may have implications for understanding the mechanisms of PVR and could provide a potential new therapeutic target for PVR prophylaxis.
增殖性玻璃体视网膜病变（PVR）仍然是视网膜脱离（RD）手术失败的主要原因，尽管发生这种并发症的风险与一些临床特征相关，但相关性远非绝对，这增加了遗传易感性的可能性。本研究的目的是分析接受 RD 手术的患者中 PVR 的遗传贡献，即 Retina 4 项目。
在 2006 年，在西班牙的一个 450 名原发性孔源性 RD 患者的人群中进行了候选基因关联研究。在几个欧洲中心接受 RD 手术的 546 名新患者中进行了更大规模的人群复制。分析了已知与炎症有关的 30 个基因的单核苷酸多态性（SNP）。在复制阶段，对先前检测到与 PVR 显著相关的基因进行了基因分型。分析了病例组和对照组中等位基因和单倍型频率的分布。评估了单倍型和单倍型分析。采用 Rosenberg 两阶段法对单因素和多因素分析进行了校正。
经过多次比较校正后，有 4 个基因与 PVR 显著相关：SMAD7（P = 0.004）、PIK3CG（P = 0.009）、TNF 基因座（P = 0.0005）和 TNFR2（P = 0.019）。在欧洲样本中，SMAD7（P = 0.047）和 TNF 基因座（P = 0.044）得到了复制。
这些结果证实了 PVR 的遗传贡献，以及 SMAD7 和 TNF 基因座在 PVR 发展中的作用。这一发现可能对理解 PVR 的机制具有重要意义，并为 PVR 预防提供潜在的新治疗靶点。
