A genetic case-control study confirms the implication of SMAD7 and TNF locus in the development of proliferative vitreoretinopathy

Jimena Rojas, Itziar Fernandez, Jose C Pastor, Robert E Maclaren, Yashim Ramkissoon, Steven Harsum, David G Charteris, Jan C Van Meurs, Sankha Amarakoon, Jose M Ruiz-Moreno, Amandio Rocha-Sousa, Maria Brion, Angel Carracedo

Research output: Contribution to journalArticleResearchpeer-review


PURPOSE: 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.

METHODS: 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.

RESULTS: 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).

CONCLUSIONS: 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.

Original languageEnglish
Pages (from-to)1665-78
Number of pages14
JournalInvestigative ophthalmology & visual science
Issue number3
Publication statusPublished - 5 Mar 2013


  • Case-Control Studies
  • Class Ib Phosphatidylinositol 3-Kinase/genetics
  • Europe
  • Female
  • Gene Frequency
  • Genotype
  • Haplotypes
  • Humans
  • Male
  • Polymorphism, Single Nucleotide
  • Receptors, Tumor Necrosis Factor, Type II/genetics
  • Retinal Detachment/surgery
  • Smad7 Protein/genetics
  • Tumor Necrosis Factor-alpha/genetics
  • Vitreoretinopathy, Proliferative/genetics


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