A Genetic Case-Control Study Confirms the Implication of SMAD7 and TNF Locus in the Development of Proliferative Vitreoretinopathy

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Rojas, J (Author) Other; Fernandez, I (Author) Other; Pastor, JC (Author) Other; MacLaren, RE (Author) Other; Ramkissoon, Y (Author) Other; Harsum, S (Author) Other; Charteris, DG (Author) Other; Van Meurs, JC (Author) Other; Amarakoon, S (Author) Other; Ruiz Moreno, JM (Author) Other; Rocha-Sousa A (Author) FMUP; Brion, M (Author) Other; Carracedo, A (Author) Other

Journal

Title: Investigative ophthalmology & visual science

Vol. 54

Pages: 1665-1678

ISSN: 0146-0404

Indexing

ISI Web of Knowledge - 36 Citations

Scopus - 37 Citations

Other information

Authenticus ID: P-005-2RY

DOI: 10.1167/iovs.12-10931

Abstract (EN): 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. (Invest Ophthalmol Vis Sci. 2013;54:1665-1678) DOI:10.1167/iovs.12-10931

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14