Abstract Details

Title An SLC9A9 Variant Influences Treatment Response in Interferon beta Treated Multiple Sclerosis Patients

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 141

Objective

Background BACKGROUND: Patients' responses to INFb may be highly heterogeneous. The early identification of the most effective MS treatment is critical to impact the long-term outcome and to move toward a personalized approach.

Design/Methods DESIGN/METHODS: A genome-wide association study was performed comparing responders vs non-responders in an Italian cohort of relapsing-remitting patients treated with IFNb. The top genetic variant was replicated in three independent collections of American, Italian and French patients and data were then meta-analyzed.

Results RESULTS: The rs9828519G allele is associated with an increased risk of non-response to IFNb therapy in the Italian MS patients (p-value=4.43x10^8). The proportion of non-responders increases for each additional copy of the G allele that is carried, suggesting an additive effect. The same allele and the same direction of effect were observed also in additional American, Italian and French patients; a meta-analysis across the three replication datasets confirmed the effect of the rs9828519 (p-value=0.0007). On the contrary, the genetic variant didn't appear to influence the response to glatiramer acetate in an independent American dataset (p-value=0.14). The genetic variant is intronic to SLC9A9, which encodes a sodium hydrogen exchanger. Preliminary results from functional studies suggest that the genetic variant may affect the expression level of SLC9A9 splice variants.

Conclusions CONCLUSIONS: Rs9828519G affects the response of MS subjects to IFNb but not to glatiramer acetate, suggesting that this genetic variant could be included into a predictive model of non-response to IFNb. We speculate that the genetic variant may affect treatment response by altering splicing sites at the intronic level. These results need to be further validated in large cohorts of IFN?-treated patients.

Authors/Disclosures
Federica Esposito PRESENTER	Federica Esposito has received personal compensation in the range of $0-$499 for serving as a Consultant for Merck. Federica Esposito has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Federica Esposito has received personal compensation in the range of $0-$499 for serving as a Consultant for Novartis. Federica Esposito has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Federica Esposito has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. The institution of Federica Esposito has received research support from Italian MS Society. The institution of Federica Esposito has received research support from Italian Ministry of Health. The institution of Federica Esposito has received research support from ERA Net. The institution of Federica Esposito has received research support from European Commission. Federica Esposito has received intellectual property interests from a discovery or technology relating to health care.
Melissa Sorosina	Melissa Sorosina has received research support from Italian Multiple Sclerosis Foundation. Melissa Sorosina has received research support from Italian Ministry of Health.
	No disclosure on file
Amber Salter, PhD (UT Southwestern Medical Center)	Dr. Salter has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gryphon Bio. Dr. Salter has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abata Therapeutics. Dr. Salter has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sora Neuroscience. Dr. Salter has stock in Owl Therapeutics. The institution of Dr. Salter has received research support from National Multiple Sclerosis Society. The institution of Dr. Salter has received research support from Department of Defense Congressionally Directed Medical Research Program. The institution of Dr. Salter has received research support from Consortium of Multiple Sclerosis Centers.
	No disclosure on file
	No disclosure on file
Jason H. Karlawish, MD	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Vittorio Martinelli (S. Raffaele Hospital)	Dr. Martinelli has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis, Biogen, Sanofi Genzyme, TEVA and Merck. Dr. Martinelli has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck .
	No disclosure on file
Giancarlo Comi, MD (University Vita-Salute)	Dr. Comi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Janssen. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Aspen Healthcare. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Sanofi. Dr. Comi has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Rewind.
Philip De Jager, MD, PhD (Columbia University Irving Medical Center)	Dr. De Jager has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Puretech. Dr. De Jager has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for roche. Dr. De Jager has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for biogen. The institution of Dr. De Jager has received research support from roche. The institution of Dr. De Jager has received research support from puretech.
Filippo Martinelli Boneschi	No disclosure on file

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