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Multiple sclerosis immunopathic trait and HLA-DR(2)15 as independent risk factors in multiple sclerosis
Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Neurologi. Linköpings universitet, Hälsouniversitetet.
Institute of Clinical Neuroscience, Sahlgrenska University Hospital, Gothenburg, Sweden.
Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Neurologi. Linköpings universitet, Hälsouniversitetet.
Sahlgrenska University Hospital, Gothenburg, Sweden.
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2007 (Engelska)Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 13, nr 4, s. 441-445Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

We analysed HLA haplotypes in pairs of 78 sporadic multiple sclerosis (MS) patients and 78 healthy siblings. The presence of 2 oligoclonal IgG bands, detected by immunoblotting of the cerebrospinal fluid in healthy siblings, has previously been defined as MS immunopathic trait (MSIT), based on a cut-off derived from healthy unrelated volunteers. The frequency of MSIT was 17.9% (n=14/78 siblings). The HLA-DR(15)2 allelle was present in 21.4% (n=3/14) of the siblings with MSIT, in 40.6% (n =26/64) of the siblings without MSIT, and in 59% (n =46/78) of the patients with clinically-definite (CD) MS. The distribution of zero, one or two HLA-DR(2)15 alleles was significantly skewed towards a lower allelle count in the siblings with MSIT compared with the group of unrelated siblings with MS (P=0.002), and also lower than their related siblings with MS (P=0.1). These results suggest that the MS susceptibility gene, HLA-DR(2)15 type, does not induce MSIT, and conceivably these are two separate risk factors in the development of MS. The effect of HLA-DR(2)15 and MSIT in sporadic MS appears to be synergistic.

Ort, förlag, år, upplaga, sidor
2007. Vol. 13, nr 4, s. 441-445
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:liu:diva-40847DOI: 10.1177/1352458506070264Lokalt ID: 54299OAI: oai:DiVA.org:liu-40847DiVA, id: diva2:261696
Tillgänglig från: 2009-10-10 Skapad: 2009-10-10 Senast uppdaterad: 2017-12-13Bibliografiskt granskad
Ingår i avhandling
1. Epidemiological and genetic studies of muliple sclerosis with focus on the Swedish county of Värmland
Öppna denna publikation i ny flik eller fönster >>Epidemiological and genetic studies of muliple sclerosis with focus on the Swedish county of Värmland
2006 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

The aim of this study was to perform detailed investigations of a presumed high-risk area, namely the county of Värmland, to see if previous results from our group indicating a high frequency of multiple sclerosis (MS) could be confirmed. We soon identified an aggregation of MS cases in the parish of Lysvik located in the north of Värmland and initiated epidemiological and genetical analyses of the population. We also extended our genetic research to include studies of a possible association between MS immunopathic trait and the MS susceptibility gene HLA-DR(2)15 type, but in another geographic area.

The onset-adjusted prevalence of MS in Värmland was 170/105 (95% CI: 154-185) in December 2002, which is higher than prevalence previously reported from other Swedish areas. There was a great variation in MS frequency between communities in Värmland. We found a persistently high occurrence of MS in Torsby and Sunne communities. In the community of Årjäng MS frequency had increased substantially since the previous study performed by our group.

Epidemiological analysis of a cluster of MS cases in Lysvik revealed 27 MS patients, of whom 23 were the descendants of a Finnish family originated from a common ancestor born in Savolaks in Finland in the 16th century and 18 had relatives with MS. Since this cluster was most likely to have a genetic basis (located in an area with a high inbreeding rate) the mode of MS inheritance was investigated. The linkage study using the genome-wide transmission disequilibrium test (TDT) provided several regions of interest, especially on chromosome 14q (14q24-31). The linkage peak on chromosome 17q was also confirmed by this study.

The frequency of the HLA-DR(2)15 allele was higher in healthy siblings of MS patients without MS immunopathic trait (MSIT) than in siblings with the trait, which provides further support for the hypothesis that MSIT and MS are two independent, albeit, synergistic conditions.

The prevalence study supports that Värmland County is a high-risk area. Furthermore, the aggregation of MS cases in Lysvik indicates a concentrated risk zone, possibly due to a combination of genetic, environmental and social risk factors. A widely and evenly spread environmental (i.e., infectious) agent together with cultural changes and industrialisation could possibly induce disease in subgroups of genetically more susceptible individuals. The evidence of linkage to chromosome 14 found in this study indicates that further genetic research is required.

Ort, förlag, år, upplaga, sidor
Linköping: Institutionen för nervsystem och rörelseorgan, 2006. s. 60
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 949
Nyckelord
Inborn genetic diseases, Genetic predisposition to disease, Genetic predisposition to disease, Cluster analysis, Muliple sclerosis, Pedigree
Nationell ämneskategori
Medicinsk genetik
Identifikatorer
urn:nbn:se:liu:diva-7444 (URN)91-85497-86-X (ISBN)
Disputation
2006-06-01, Elsa Brändströms sal, Södra ingången, plan 10, Campus US, Linköpings Universitet, Linköping, 13:00 (Engelska)
Opponent
Tillgänglig från: 2006-09-27 Skapad: 2006-09-27 Senast uppdaterad: 2018-01-13Bibliografiskt granskad

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Callander, MargaritaLandtblom, Anne-Marie

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