| 1. |
- Helgadottir, Anna, et al.
(författare)
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The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:2, s. 217-224
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Tidskriftsartikel (refereegranskat)abstract
- Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD)(1-4) and type 2 diabetes (T2D)(5-7), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.
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| 2. |
- Jons, Daniel, et al.
(författare)
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Epstein-Barr virus seroreactivity, putative autoimmunity and axonal injury in pre-symptomatic multiple sclerosis
- 2023
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 29:Suppl. 3, s. 39-40
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Multiple sclerosis (MS) and presymptomatic axonal injury appears to develop only after an Epstein-Barr virus (EBV) infection. Anoctamin2 (ANO2), a chloride channel expressed in glial cells and neurons, was identified as a possible MS autoantigen. We here examine serum neurofilament (sNfL), a comprehensive EBV seroreactivity and antibodies against ANO2 in pre-symptomatic MS.Objectives/Aims: To study whether the appearance of EBV seroreactivity in the pre-symptomatic phase of MS precedes cumulating MS-induced neuroaxonal damage and whether it is associated with an incipient autoreactivity against a reported MS autoantigen (ANO2).Methods: We performed a case-control study with presymptomatic serum samples identified through cross-linkage of the Swedish MS register and Swedish biobanks. We assayed serum antibodies against EBV nuclear antigen 1 (EBNA1), viral capsid antigen p18 (VCAp18), EBV glycoprotein 350 (gp350), anoctamin 2 (ANO2), and serum neurofilament light (sNfL) in 669 pre-MS cases and matched controls.Results: EBNA1 seroreactivity increased in the pre-MS group from 20–15 years before MS onset, followed by gp350 seroreactivity (p=0.001–0.002, 15–10 years before onset). This appeared before the elevation of sNfL in EBV seropositive pre-MS cases (p=8⋅10-5, 10–5 years before onset). No significant sNfL increase was observed in the EBV seronegative group (p=0.95). Pre-MS cases with the highest sNfL levels cumulated in the EBV seropositive group (p=0.038). ANO2 seropositivity appeared virtually only in the EBNA1 seropositive group, in 16.7 % of EBNA1 seropositive pre-MS samples and in 10.0 % of corresponding controls (p=0.001). Combined EBNA1 and ANO2 seropositivity showed a higher association with subsequent MS than EBNA1 independent of ANO2 (p=0.002–0.028). In the EBNA1 seropositive stratum, ANO2 seropositivity was associated with 26% higher sNfL.Conclusion: In presymptomatic MS an antibody response against EBV, associated with ANO2 autoimmunity, was detectable before elevated sNfL, which cumulated in the EBV seropositive group. ANO2 seropositivity was associated with higher sNfL. An increase in ANO2 seroreactivity did not appear until after EBV seroconversion, limited to a subgroup of the EBV seropositive stratum. Thus, this specific cross-reaction could contribute to MS pathogenesis in a subgroup. This further implicates EBV in the pathogenesis of MS.
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| 3. |
- Ahlgren, Cecilia, 1946, et al.
(författare)
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A population-based case-control study on viral infections and vaccinations and subsequent multiple sclerosis risk.
- 2009
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 24:9, s. 541-52
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Tidskriftsartikel (refereegranskat)abstract
- Viral infections are probably involved in the pathogenesis of multiple sclerosis (MS). A recent cohort study in the Gothenburg population revealed no change in MS incidence associated with the introduction of the Swedish measles, mumps and rubella vaccination programmes. The aim of the present study was to clarify whether these infections or vaccinations, and two other infections, varicella and infectious mononucleosis, influence MS risk. We performed a population-based case-control study in Gothenburg that included 509 MS cases and 2,067 controls, born 1959-1986. Data on infections and vaccinations were obtained from questionnaires and from child health and school health records. We found no significant associations between measles, mumps, rubella or varicella and MS risk. These results were consistent between the two source materials. Infectious mononucleosis was associated with significantly higher MS risk (odds ratio 2.03, 95% CI 1.52-2.73). Overall, there was no significant association between measles-mumps-rubella (MMR) vaccination and MS risk, while those MMR vaccinated before age ten only were at significantly higher MS risk (odds ratio 4.92, 95% CI 1.97-12.20). Those MMR vaccinated both before and after age ten had intermediate MS risk. Infection with measles, mumps, rubella and varicella did not influence MS risk in contrast to infectious mononucleosis which conferred doubled MS risk. The association with 'early' MMR vaccination only was an isolated finding, limited by a small number of subjects and multiple testing. Most likely this was a chance finding. Future studies could investigate it on an a priori basis.
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| 4. |
- Ahlgren, Cecilia, 1946, et al.
(författare)
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High risk of MS in Iranian immigrants in Gothenburg, Sweden.
- 2010
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Ingår i: Multiple sclerosis journal. - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 16:9, s. 1079-1082
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In this study we investigated the risk of multiple sclerosis (MS) in migrants who had moved from Iran to Gothenburg, Sweden. METHODS: Patients born in Iran were retrieved from a population-based cohort, which included 534 MS and clinically isolated syndrome patients, born 1959-1990, aged 10-39 years at disease onset in Gothenburg. The expected versus observed number of migrants from Iran was calculated. RESULTS: The MS risk in the Iranian migrants in Gothenburg was several times higher than in Isfahan, Iran (hazard ratio 3.88, 95% confidence interval 2.17-6.40). Compared with the general population of Gothenburg, the observed number of 17 Iranian patients was higher than the expected value of 9.89 (hazard ratio 1.72, 95% confidence interval 1.00-2.75). CONCLUSION: Migration from a medium-risk to a high-risk area may increase the MS risk to that of the high-risk area.
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| 5. |
- Ahlgren, Cecilia, 1946, et al.
(författare)
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Multiple sclerosis incidence in the era of measles-mumps-rubella mass vaccinations.
- 2009
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Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 119:5, s. 313-20
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Viral childhood infections may be involved in the multiple sclerosis (MS) pathogenesis. Following national Swedish vaccination programs, measles sharply declined in the 1970s, and measles, mumps, and rubella were virtually eliminated in cohorts born from 1981. OBJECTIVES: To examine whether the vaccination induced reduction in these infections influences the MS incidence. In addition, the public health aspect justified an early evaluation of beneficial as well as harmful effects of mass vaccinations. MATERIALS AND METHODS: From an incidence material of 534 MS patients, born 1959-1990, we selected one unvaccinated cohort and four cohorts, each corresponding to a vaccination program (MS patients = 251). RESULTS: With the ability to detect a decrease by 30-35%, and an increase by 37-48% in the MS incidence in the first three cohorts, we found no vaccination related MS incidence changes. The background MS incidence showed a significant gradual age dependent increase. CONCLUSIONS: While the present follow-up provided limited power in the last cohort, there is no evidence as yet that the radical decline in three viral infections influenced the MS incidence. However, the increasing background MS incidence of unknown cause may have concealed a reduction in MS risk associated with mass vaccinations.
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| 6. |
- Ahlgren, Cecilia, 1946, et al.
(författare)
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No major birth order effect on the risk of multiple sclerosis
- 2005
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Ingår i: Neuroepidemiology. ; 24, s. 38-41
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Tidskriftsartikel (refereegranskat)abstract
- Abstract In the present study, we found no association between multiple sclerosis (MS; definite and probable, n = 211) and birth order (p = 0.1411). The observed number of first-born patients did not differ significantly from the expected number (p = 0.0871). While there was a significantly high birth order (n = 258, p = 0.0381) and a marginally significant low number of first-borns (p = 0.0475) when possible MS cases were included, an artefact due to the population structure may have accentuated this result. In comparison with the control birth cohort, there was no significant association with birth order (p = 0.0742) or the proportion of first-borns (p = 0.220) in a subgroup from the MS incidence cohort born between 1915 and 1929 (n = 158). Birth order had no major impact on the risk of subsequent MS in this study. Copyright © 2005 S. Karger AG, Basel
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| 7. |
- Ahlgren, Cecilia, 1946, et al.
(författare)
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The effect of live, attenuated measles vaccine and measles infection on measles antibody levels in serum and CSF of patients with multiple sclerosis or clinically isolated syndrome.
- 2011
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Ingår i: Journal of neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 235:1-2, s. 98-103
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Tidskriftsartikel (refereegranskat)abstract
- High occurrence of measles, rubella and varicella zoster antibodies has been used as a biomarker for MS (the MRZ test). We analyzed measles antibody titres with respect to measles infection/measles vaccination status in 166 patients with MS or clinically isolated syndrome. Fifty blood donors served as controls. Measles vaccination yielded CSF measles antibodies in fewer patients (62%) than measles infection did (87%, p=0.001) and yielded lower measles titres in both serum and CSF (p<0.001). Controls had lower CSF measles titres than patients with measles vaccination alone (p<0.001). Childhood vaccinations probably reduce the sensitivity of the MRZ diagnostic test for MS.
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| 8. |
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| 9. |
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| 10. |
- Andersen, Oluf, 1941, et al.
(författare)
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Diffusion tensor imaging in multiple sclerosis at different final outcomes
- 2018
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 137:2, s. 165-173
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES:Methods to evaluate the relative contributions of demyelination vs axonal degeneration over the long-term course of MS are urgently needed. We used magnetic resonance diffusion tensor imaging (DTI) to estimate degrees of demyelination and axonal degeneration in the corpus callosum (CC) in cases of MS with different final outcomes.MATERIALS AND METHODS:We determined DTI measures mean diffusivity (MD), fractional anisotropy (FA), and axial (AD) and radial (RD) diffusivities in the CC of 31 MS patients, of whom 13 presented a secondary progressive course, 11 a non-progressive course, and seven a monophasic course. The study participants were survivors from an incidence cohort of 254 attack-onset MS patients with 50 years of longitudinal follow-up. As reference, we included five healthy individuals without significant morbidity.RESULTS:In patients with secondary progression, compared to all other groups, the corpus callosum showed increased RD and reduced FA, but no change in AD. None of the parameters exhibited differences among non-progressive and monophasic course groups and controls.CONCLUSION:Increased RD was observed in secondary progressive MS, indicating significant myelin loss. Normal RD values observed in the clinically isolated syndrome and non-progressive groups confirm their benign nature. AD was not a characterizing parameter for long-term outcome. Demyelination revealed by increased RD is a distinguishing trait for secondary progression.
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