The Influence of Host Genetics on JCV and EBV Antibody Levels in Multiple Sclerosis Patients and Controls
Independent thesis Advanced level (degree of Master (Two Years)), 40 credits / 60 HE creditsStudent thesis
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), characterized by lesions formed due to demyelination. MS is a complex disease thought to be triggered by environmental factors in genetically predisposed individuals. The strongest associated susceptibility allele is HLA-DRB1*1501. Environmental factors include smoking, latitude and previous infection of Epstein-Barr virus (EBV), a common herpes virus. There is no cure for MS, but several inhibitor and symptomatic drugs. Tysabri® (natalizumab) is the most effective drug, but it may lead to progressive multifocal leukoencephalopathy (PML), a rare but often fatal disease caused by reactivation of JC virus.
The aim of this thesis was to replicate previous findings from a genome-wide association study and to find host genetic factors influencing JCV seropositivity and EBNA1 IgG titers in Swedish MS patients and healthy controls. Samples from the EIMS and IMSE studies were genotyped by TaqMan® OpenArray™ PCR, an end-point SNP genotyping analysis. 1143 cases and 556 healthy controls were genotyped. Due to poor call rates, genotype data from an Immunochip study was added. A total of 3408 samples (1664 cases and 1744 controls) were analyzed. EBNA1 IgG antibodies were previously measured as a detection of EBV infection and increased MS risk, and JCV IgG antibodies were measured to find patients potentially at risk for PML.
One significant result was found, gene 105 (p = 0.01674, OR 0.68, CI 95% 0.49-0.93), with a protective effect in MS. More significant results might have been found with better loading of the plate, or with a different genotyping method.
Place, publisher, year, edition, pages
2012. , 47 p.
Host genetics, multiple sclerosis, EBV, JCV, natalizumab, OpenArray, genotyping
IdentifiersURN: urn:nbn:se:liu:diva-85459ISRN: LITH-IFM-A-EX--12/2582—SEOAI: oai:DiVA.org:liu-85459DiVA: diva2:570506
CMM, Karolinska Institutet, Solna
Subject / course
2012-08-24, bikupan, Linköpings Universitet, 85183 Linköping, Linköping, 15:37 (Swedish)
UppsokPhysics, Chemistry, Mathematics
Mårtensson, Lars-Göran, Accociate professor
Mårtensson, Lars-Göran, associate professor