No evidence of association of the rare nsSNP rs35667974 in IFIH1 with multiple sclerosis

Bergamaschi, Laura; Ban, Maria; Leone, Maurizio A.; Sawcer, Stephen J.; D'Alfonso, Sandra

doi:10.1016/j.jneuroim.2010.01.005

« Previous Next »Journal of Neuroimmunology
Volume 221, Issue 1 , Pages 112-114, 15 April 2010

No evidence of association of the rare nsSNP rs35667974 in IFIH1 with multiple sclerosis

Laura Bergamaschi
- Department of Medical Sciences and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Novara, Italy
- Corresponding author. Department of Medical Sciences, Eastern Piedmont University, Via Solaroli 17, 28100 Novara, Italy. Tel.: +39 0321 660606; fax: +39 0321 620421.
Maria Ban
- University of Cambridge, Department of Clinical Neuroscience, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK
Maurizio A. Leone
- Department of Neurology, Ospedale Maggiore della Carità, and IRCAD, Novara, Italy
Stephen J. Sawcer
- University of Cambridge, Department of Clinical Neuroscience, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK
Sandra D'Alfonso
- Department of Medical Sciences and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Novara, Italy

Received 12 November 2009; received in revised form 11 January 2010; accepted 11 January 2010. published online 01 February 2010.

Abstract

Studies suggest that different autoimmune diseases share a common genetic background, in particular, an overlap between Multiple Sclerosis (MS) and type 1 diabetes (T1D) susceptibility loci has been established. A recent study found that four rare SNPs in the IFIH1 (interferon induced with helicase C domain 1) were significantly associated with T1D.

To establish if these SNPs were also involved in MS susceptibility, we chose to examine the non-synonymous SNP rs35667974/Ile923Val which displayed the strongest effect in T1D and was also shown to lead to a loss of IFIH1 function in an in vitro study. We have performed the first association study to test if this rare variant is involved in MS susceptibility in a very large sample consisting of 3037 MS patients and 10,657 healthy controls recruited from Italy and the UK. This study has 99% power to demonstrate an association at the 5% level with this rare variant. Our analysis shows that the nsSNP rs35667974/Ile923Val does not have a role in susceptibility to MS.

Keywords: Multiple Sclerosis, Genetics, IFIH1