Chromosome 19q13 and multiple sclerosis susceptibility in Finland: a linkage and two-stage association study

Reunanen, Karoliina; Finnilä, Saara; Laaksonen, Mikko; Sumelahti, Marja Liisa; Wikström, Juhani; Pastinen, Tomi; Kuokkanen, Satu; Saarela, Janna; Uimari, Pekka; Ruutiainen, Juhani; Ilonen, Jorma; Peltonen, Leena; Tienari, Pentti J.

doi:10.1016/s0165-5728(02)00051-6

Cited by 24 publications

(22 citation statements)

References 38 publications

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“…In various genes, the apolipoprotein E (APOE) gene, which is located in the chromosome 19q13.2 region and codes for ApoE, has been one of the most studied in the past [8,9]. ApoE is a glycoprotein synthesized in the CNS by glial cells which has a crucial role in membrane remodeling and repair, as well as an immunomodulatory effect [10].…”

Section: Introductionmentioning

confidence: 99%

No association between APOE epsilon 4 allele and multiple sclerosis susceptibility: A meta-analysis from 5472 cases and 4727 controls

Xuan

Zhang

et al. 2011

Journal of the Neurological Sciences

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Section: Introductionmentioning

confidence: 99%

No association between APOE epsilon 4 allele and multiple sclerosis susceptibility: A meta-analysis from 5472 cases and 4727 controls

Xuan

Zhang

et al. 2011

Journal of the Neurological Sciences

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“…At present, we cannot resolve this issue. However, certain previous association 32 and linkage signals 27,33,34 have been obtained only in the HLA-DRX MS group, indicating that this HLA dichotomy may be either biologically or genealogically sound.…”

Section: Multiple Sclerosis and 2q33mentioning

confidence: 97%

“…27 Five markers were included: D2S2396, D2S116, D2S72, D2S1271 and D2S422 (see Figure 1). No statistically significant evidence for linkage was found.…”

Section: à10mentioning

confidence: 99%

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A two-stage study on multiple sclerosis susceptibility and chromosome 2q33

et al. 2004

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We have performed a two-stage study to analyse the association of polymorphism on chromosome 2q33 with multiple sclerosis (MS). In all, 17 markers were analysed in stage-1 in 134 Finnish MS families and the observed associations were tested in stage-2 in 186 MS families. We did not find previously reported allelic or haplotype associations with CTLA4. We obtained a weak signal of two distinct predisposing genes, one proximal the other distal of CTLA4. The putative proximal gene was associated with the marker rs3977 in families lacking HLA-DR2 (P ¼ 0.02 and 0.02) and the other distal gene was associated with D2S1271 in families from a high-risk region in western Finland (P ¼ 0.02 and 0.01). Based on the 43 cM distance and the lack of linkage disequilibrium between these loci, we conclude that the two association signals are independent. Our results provide preliminary evidence for two distinct MS susceptibility genes on 2q33 outside of CTLA4.

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“…5 Whole genome linkage screens indicate that there is no single major gene but multiple loci with relatively weak effects. A few chromosomal regions, besides HLA, have been supported by two or more genome-wide or more targeted studies, [6][7][8][9][10][11][12][13] but the chromosomal regions harboring the putative susceptibility genes are still relatively wide. In addition, candidate gene association studies have suggested some potential predisposing loci, but these have not been uniformly confirmed.…”

Section: Introductionmentioning

confidence: 99%

Linkage disequilibrium between the MBP tetranucleotide repeat and multiple sclerosis is restricted to a geographically defined subpopulation in Finland

et al. 2003

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We have previously found evidence for linkage as well as allelic and haplotype association between the myelin basic protein (MBP) gene and multiple sclerosis (MS). These findings have, however, not been reproduced in other populations. Here, we have analyzed association between MBP and MS in a new set of 349 Finnish triad families. Families with a parent born in the Southern Ostrobothnian region in western Finland (Bothnia families, n ¼ 98) were analyzed as a separate group since our previous studies included a high proportion of patients and families from this high-incidence region. Other families (n ¼ 251) were collected at five hospitals in southern, eastern, and northern Finland. The MBP short tandem repeat was genotyped, and haplotype patterns were verified by sequencing. In the Bothnia families, the previously detected associations with the 1.27 kb allele and haplotype 1.27-B10 were confirmed (P ¼ 0.01 and 0.02, respectively), whereas in the other families there was not even a trend toward association. These results demonstrate a geographic/genealogical restriction in the association between MS and the MBP short tandem repeat, highlight the importance of genealogical information in genetic studies of complex traits, and may provide an explanation why the association has not been found in many other populations.

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Chromosome 19q13 and multiple sclerosis susceptibility in Finland: a linkage and two-stage association study

Cited by 24 publications

References 38 publications

No association between APOE epsilon 4 allele and multiple sclerosis susceptibility: A meta-analysis from 5472 cases and 4727 controls

No association between APOE epsilon 4 allele and multiple sclerosis susceptibility: A meta-analysis from 5472 cases and 4727 controls

A two-stage study on multiple sclerosis susceptibility and chromosome 2q33

Linkage disequilibrium between the MBP tetranucleotide repeat and multiple sclerosis is restricted to a geographically defined subpopulation in Finland

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