MIF promoter polymorphism variations in retinal detachment with proliferative vitreoretinopathy

Abstract

Purpose : Pro-inflammatory factors promote development of proliferative vitreoretinopathy (PVR) in retinal detachment (RD). We tested the hypothesis that promoter polymorphisms that influence expression of the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) are associated with PVR development.

Methods : A multi-center prospective study of 284 American RD patients with PVR (n=114) and without PVR (n= 170) and local unaffected controls (n=202) was conducted under an IRB-approved protocol. Blood samples, vitreous surgical specimens when available, and clinical data were collected. Germline DNA was extracted from mononuclear cells at the OSU Human Cancer Genetic sample bank. Two polymorphisms, rs755622 (previously reported as -173G>C) and rs5844572 (previously reported as -794 (CATT)_5-8) were evaluated with allele-specific primer PCR and sequencing; frequencies of genotypes, alleles, and the C7 haplotype were compared in patients with data (n=137 RD and 74 RD-PVR). Chi-square and Fisher exact analysis was performed and odds ratios calculated.

Results : There was no significant difference between the frequency of the MIF polymorphisms in unaffected regional controls and the RD population. In the RD patients, the C allele of rs755622 was found to be less frequent in RD-PVR than in RD (odds ratio [95% confidence intervals]=0.5456 [0.3146-0.9462]; p=0.0310). The rs5844572 7 allele was also lower in RD-PVR patients (5.4%) vs RD (15%) (p=0.0237). Fisher exact test showed a significant decreased frequency of the C7 haplotype in RD-PVR patients compared to RD. The odds ratio of C7 = 0.3401 [0.1488-0.7772]; p=0.0105.

Conclusions : Specific MIF promoter polymorphisms may influence the development of PVR in patients with RD. Further studies to evaluate MIF’s role in the retina are needed.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.