11 research outputs found
Genome Wide Association Identifies PPFIA1 as a Candidate Gene for Acute Lung Injury Risk Following Major Trauma
Acute Lung Injury (ALI) is a syndrome with high associated mortality characterized by severe hypoxemia and pulmonary infiltrates in patients with critical illness. We conducted the first investigation to use the genome wide association (GWA) approach to identify putative risk variants for ALI. Genome wide genotyping was performed using the Illumina Human Quad 610 BeadChip. We performed a two-stage GWA study followed by a third stage of functional characterization. In the discovery phase (Phase 1), we compared 600 European American trauma-associated ALI cases with 2266 European American population-based controls. We carried forward the top 1% of single nucleotide polymorphisms (SNPs) at p<0.01 to a replication phase (Phase 2) comprised of a nested case-control design sample of 212 trauma-associated ALI cases and 283 at-risk trauma non-ALI controls from ongoing cohort studies. SNPs that replicated at the 0.05 level in Phase 2 were subject to functional validation (Phase 3) using expression quantitative trait loci (eQTL) analyses in stimulated B-lymphoblastoid cell lines (B-LCL) in family trios. 159 SNPs from the discovery phase replicated in Phase 2, including loci with prior evidence for a role in ALI pathogenesis. Functional evaluation of these replicated SNPs revealed rs471931 on 11q13.3 to exert a cis-regulatory effect on mRNA expression in the PPFIA1 gene (p = 0.0021). PPFIA1 encodes liprin alpha, a protein involved in cell adhesion, integrin expression, and cell-matrix interactions. This study supports the feasibility of future multi-center GWA investigations of ALI risk, and identifies PPFIA1 as a potential functional candidate ALI risk gene for future research
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Dislocation of the donor graft to the posterior segment in descemet stripping automated endothelial keratoplasty
To report a series of dislocations of the donor graft into the posterior segment associated with Descemet stripping endothelial keratoplasty (DSAEK) and to identify possible risk factors for dislocation and clinical outcomes.
Retrospective case series.
Cases of donor graft dislocation into the posterior segment associated with endothelial keratoplasty were identified from the clinical experience of 7 surgeons. Observations included the preoperative surgical history of each eye, preoperative and postoperative visual acuity, management of the complication, and the postoperative clinical course. No identified cases were excluded from this series.
Eight posterior graft dislocations were associated with DSAEK surgery. Each eye had a history of vitrectomy. Five eyes had sutured posterior chamber intraocular lenses, 1 eye had a sulcus intraocular lens, and 2 eyes were aphakic. Each eye required repeat grafting, and in 6 of 8 eyes, pars plana vitrectomy was used to remove the dislocated graft. Final visual acuities ranged from 20/30 to no light perception.
Graft dislocation into the posterior segment is a rare complication of DSAEK surgery that can lead to permanent vision loss. It has occurred in eyes that have undergone previous vitrectomy and complicated intraocular lens placement or were aphakic. As is the case with a dropped lens nucleus during cataract extraction, visual acuities after a dropped DSAEK graft range from very good to no light perception. Better postoperative results seem to be associated with prompt removal of the posteriorly dislocated graft
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The Effect of Donor Age on Penetrating Keratoplasty for Endothelial Disease Graft Survival after 10 Years in the Cornea Donor Study
ObjectiveTo determine whether the 10-year success rate of penetrating keratoplasty for corneal endothelial disorders is associated with donor age.DesignMulticenter, prospective, double-masked clinical trial.ParticipantsA total of 1090 participants undergoing penetrating keratoplasty at 80 sites for Fuchs' dystrophy (62%), pseudophakic/aphakic corneal edema (34%), or another corneal endothelial disorder (4%) and followed for up to 12 years.MethodsForty-three eye banks provided corneas from donors aged 12 to 75 years, using a randomized approach to assign donor corneas to study participants without respect to recipient factors. Surgery and postoperative care were performed according to the surgeons' usual routines.Main outcome measuresGraft failure defined as a regraft or, in the absence of a regraft, a cloudy cornea that was sufficiently opaque to compromise vision for 3 consecutive months.ResultsIn the primary analysis, the 10-year success rate was 77% for 707 corneas from donors aged 12 to 65 years compared with 71% for 383 donors aged 66 to 75 years (difference, +6%; 95% confidence interval, -1 to +12; P = 0.11). When analyzed as a continuous variable, higher donor age was associated with lower graft success beyond the first 5 years (P<0.001). Exploring this association further, we observed that the 10-year success rate was relatively constant for donors aged 34 to 71 years (75%). The success rate was higher for 80 donors aged 12 to 33 years (96%) and lower for 130 donors aged 72 to 75 years (62%). The relative decrease in the success rate with donor ages 72 to 75 years was not observed until after year 6.ConclusionsAlthough the primary analysis did not show a significant difference in 10-year success rates comparing donor ages 12 to 65 years and 66 to 75 years, there was evidence of a donor age effect at the extremes of the age range. Because we observed a fairly constant 10-year success rate for donors aged 34 to 71 years, which account for approximately 75% of corneas in the United States available for transplant, the Cornea Donor Study results indicate that donor age is not an important factor in most penetrating keratoplasties for endothelial disease
Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error
10.1016/j.ajhg.2013.06.016American Journal of Human Genetics932264-277AJHG