Abstract Details

Title The rs10191329 Risk Allele is Associated with Retinal Layer Thinning in Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) P6 - Poster Session 6 (11:45 AM-12:45 PM)

Poster/Presentation
Number 1-013

Objective

To investigate whether the rs10191329 variant is associated with retinal layer thinning in relapsing multiple sclerosis (MS).

Background

The minor allele of the genetic variant rs10191329 in the DYSF–ZNF638 locus, which is implicated in CNS resilience rather than immune-mediated pathology, has been associated with faster disability progression in MS. Retinal layer thinning measured by optical coherence tomography (OCT) is an established biomarker of neuroaxonal damage.

Design/Methods

From a prospective observational study, we included patients with RMS and ≥2 OCT scans excluding eyes with optic neuritis during the observation period.

DNA samples were genotyped on an Illumina Infinium Global Screening Array-24 (GSA v3.0+MD) imputing individual variants onto the Haplotype Reference Consortium panel (Release 1.1) using Minimac4 (V1.0.2).

We used a multivariate linear regression model with mean annualized rates of retinal layer thinning (%/year) in peripapillary retinal nerve fiber layer (aLpRNFL) and macular ganglion-cell-and-inner-plexiform-layer (aLGCIPL) thinning as the dependent variable and rs10191329 risk allele number (rs10191329*A) as the independent variableadjusting for age, sex and 10 ancestry components.

Results

We included 208 RMS patients (mean age 30.5 years [SD 7.9], 74.1% female, median EDSS 2.0 [range 0-6.5], median observation period 25 months [range 12-105], median number of OCT scans 3 [2-6]).

We found that the risk allele of rs10191329 was associated with higher rates of retinal thinning (estimate 0.119 [standard error 0.056], one-sided p <0.001).

Each rs10191329*A allele was associated with an increase of aLpRNFL by 0.10%/year (95% confidence interval [CI] 0.05-0.19, p<0.001) and aLGCIPL by 0.11%/year (95% confidence interval [CI] 0.07-0.19, p<0.001) corresponding to 26.4% (CI 13.1-44.2) and 27.2% (CI 14.3-43.1) of mean atrophy rates (aLpRNFL 0.42%/y [0.31-0.59], aLGCIPL 0.21%/y [0.15-0.29]).

Conclusions

Carriers of the minor allele of rs10191329 seem more prone to MS-related tissue damage. While clinical implications are currently unclear, stratification for this genotype in clinical trials may be reasonable.

Authors/Disclosures
Gabriel Bsteh, MD (Medical University Vienna, Department of Neurology) PRESENTER	Dr. Bsteh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Bsteh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Bsteh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Bsteh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Bsteh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva. Dr. Bsteh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi.
Nik Krajnc, MD, PhD	No disclosure on file
Fabian Föttinger	Dr. Föttinger has nothing to disclose.
Theresa Koenig, PhD	Dr. Koenig has nothing to disclose.
Martin Krenn, MD (Medical University of Vienna)	Dr. Krenn has nothing to disclose.
Markus Ponleitner	Markus Ponleitner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amicus Therapeutics, Inc.. Markus Ponleitner has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amicus Therapeutics Inc.. Markus Ponleitner has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Markus Ponleitner has received research support from European Academy of Neurology.
Harald Hegen, MD	Dr. Hegen has nothing to disclose.
Berthold Pemp, MD (Medical University of Vienna)	Dr. Pemp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Chiesi. Dr. Pemp has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Chiesi. Dr. Pemp has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GenSight. The institution of Dr. Pemp has received research support from Chiesi.
Thomas A. Berger, MD (Dept. of Neurology, Medical University of Vienna)	Prof. Berger has received personal compensation in the range of $10,000-$49,999 for serving as a speaker at scientific meetings and participant of local and international advisory boards with various companies producing and markerting treatments for multiple sclerosis (Almirall, Biogen, Biologix, Bionorica, Celgene-BMS, Merck, Novartis, Roche, Sanofi-Genzyme, TG Therapeutics, UCB).

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