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- Modin, H, et al.
(author)
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Genome-wide linkage screen of a consanguineous multiple sclerosis kinship
- 2003
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In: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 9:2, s. 128-134
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Journal article (peer-reviewed)abstract
- Multiple sclerosis (MS), like A lzheimer’s disease (A D) and Parkinson’s disease (PD), is a common neurological disorder thought to be caused by the interaction of several genes with unknown environmental factors. In both A D and PD the identification of disease forms inherited in a classic Mendelian fashion has helped investigators elucidate pathogenetic mechanisms. In this study a whole-genome screen, with an average of 608 successful genotypes per person, was performed on nine members of a consanguineous family: the index case, three of her siblings and her daughter, all of whom have been diagnosed with definite MS; as well as the parents of the index case (first cousins), one of her five healthy siblings and her husband (who is also her first cousin). Nonparametric linkage analysis was performed on genotyping data. Based on the presence of consanguinity, the a priori hypothesis was that the disease is transmitted in an autosomal recessive fashion in the pedigree. Linkage analysis revealed a suggestive logarithm of odds (LO D) score of 2.29 on the long arm of chromosome 9. Four of five affected family members were identically homozygous for a haplotype under this peak, spanning approximately 43 cM, while the fifth affected subject and all unaffected family members were hetero zygous for the haplotype.
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- Dai, Y, et al.
(author)
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Analysis of an interferon-gamma gene dinucleotide-repeat polymorphism in Nordic multiple sclerosis patients
- 2001
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In: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 7:3, s. 157-163
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Journal article (peer-reviewed)abstract
- The proinflammatory cytokine interferon (IFN)-γ has been shown to influence the course of multiple sclerosis (MS). The IFN-γ (IFNG) contains a multiallelic dinucleotide repeat in intron l. To investigate whether alleles at this locus influence susceptibility to MS, we performed linkage and familial association analyses on 100 sibling pairs from four Nordic countries, and case-control association analysis on 220 intermediately disabled sporadic MS patients and 266 controls. To determine the effect of the polymorphism on disease outcome, we compared genotype frequencies in the most and least disabled octiles of a total cohort of 913 cases. We also measured IFN-γ mRNA levels in unstimulated peripheral blood mononuclear cells from 46 MS patients and 27 controls grouped according to IFNG intron l genotype. Both nonparametric linkage analysis and transmission disequilibrium testing of the 100 sibling pairs produced negative results. Genotype frequencies for intermediate-MS patients did not differ significantly from those for controls; nor did genotype frequencies in the benign-MS octile differ significantly from those in the severe-MS octile. Comparison of IFN-γ mRNA levels in genotype-conditioned subgroups revealed no significant differences. Thus, alleles at the IFNG intron l dinucleotide repeat appear to affect neither MS susceptibility and severity nor IFN-γ mRNA expression in vivo.
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- Henriksson, F., et al.
(author)
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Costs, quality of life and disease severity in multiple sclerosis: a cross-sectional study in Sweden
- 2001. - Received 29 March 2000 Accepted 29 September 2000
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In: European journal of neurology. - : Blackwell Science Ltd. - 1468-1331 .- 1351-5101. ; 8:1, s. 27-35
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Journal article (peer-reviewed)abstract
- This study assessed the cost to society of multiple sclerosis (MS) in Sweden in 1998. The cost-of-illness method, based on the human capital theory, was used as the theoretical framework. The study used a cross-sectional approach, in which resource utilization data and quality-of-life data (utilities) were collected at a single time point. The total cost of MS was estimated at 4868 MSEK, or 586 MEUR, giving an annual cost of 442 500 SEK, or 53 250 EUR, per patient (1USD = 9.73 SEK, 1 EUR = 8.31 SEK, as of 21 September 2000). Direct costs accounted for about 67% of total cost, and they were dominated by the cost of personal assistants and drugs. Indirect costs (loss of production) accounted for about 33% of total costs. To these economic costs, intangible costs of 2702 MSEK (325 MEUR) should be added as well. Direct, indirect and informal care costs all rose significantly with increased disability and were higher during a relapse. Quality of life declined substantially with increased disability and was lower during a relapse. Multiple sclerosis was found to be associated with much higher costs to society than has been ascertained by former studies. The study also revealed a strong correlation between severity of the disease and quality of life. These results are crucial for further studies on the cost-effectiveness of new treatments aimed at preventing relapses and reducing progression of the disease.
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- Masterman, T, et al.
(author)
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APOE genotypes and disease severity in multiple sclerosis
- 2002
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In: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 8:2, s. 98-103
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Journal article (peer-reviewed)abstract
- Apolipoprotein E (apoE) is involved in the transport of lipids necessary for membrane repair and is encoded by a gene on chromosome 19q13, a region positive for linkage in two multiple sclerosis (MS) genome-wide screens. The APOE e4 allele confers susceptibility to both familial and sporadic Alzheimer’s disease (AD). Carriage of e4 is associated with defective dendritic remodeling in AD, and with unfavorable clinical outcome in head trauma and cerebrovascular disease. According to the results of previous studies, APOE e4 does not increase the risk of developing MS, but it may influence disease progression and ultimate disability. From a total cohort of over 900 MS patients, we compared APOE e2-4 genotypes in, roughly, the cohort’s least disabled and most disabled septiles. ‘Benign MS’ (n=124) was defined as an Expanded Disability Status Scale (EDSS) score of 3.0 or less, despite at least 10 years of disease duration, and ‘severe MS’ (n=140) as the attainment of an EDSS score of 6.0 within 8 years of disease onset. We found no significant differences in genotype or phenotype frequencies between the benign-MS and severe-MS septiles; however, the risk conferred by e4 rose progressively upon comparison of carriage rates in more narrowly defined anti-podal quantiles.
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