6533b873fe1ef96bd12d4cdc
RESEARCH PRODUCT
APOE epsilon variation in multiple sclerosis susceptibility and disease severity: some answers
Reinhold SchmidtBeata Zakrzewska-pniewskaW. E. R. OllierAlastair CompstonRita CittadellaHelena SchmidtJonathan L. HainesStephen SawcerRichard M. BurwickS. J. M. WeatherbyHubert KwiecińskiPatricia P. RamsayChristian EnzingerLisa F. BarcellosLisa F. BarcellosLisa F. BarcellosMasaaki NiinoNikos EvangelouJacqueline PalaceChris H. PolmanSeiji KikuchiFranz FazekasAldo QuattroneAldo QuattroneJ. ZwemmerPeter HøghMargaret A. Pericak-vanceJan HillertBernard M. J. UitdehaagStephen L. HauserMaria Edite RioGiovanni SavettieriSilke SchmidtMónica SantosPatrícia MacielJorge R. OksenbergC. P. HawkinsThomas Mastermansubject
Apolipoprotein EOncologyRiskmedicine.medical_specialtyPathologyMultiple SclerosisGenotypeApolipoprotein E2Apolipoprotein E4Polymorphism Single NucleotideSeverity of Illness IndexLinkage DisequilibriumPrimary progressiveCentral nervous system disease03 medical and health sciences0302 clinical medicineApolipoproteins EDisease severityPolymorphism (computer science)Internal medicineGenotypemedicineHumansGenetic Predisposition to Disease10. No inequalityAlleles030304 developmental biology0303 health sciencesExpanded Disability Status ScalePolymorphism GeneticScience & Technologybusiness.industryMultiple sclerosismedicine.disease3. Good healthPedigreePhenotypeCase-Control StudiesSettore MED/26 - NeurologiaNeurology (clinical)businessMultiple Sclerosis APOE disease severity meta-analysis030217 neurology & neurosurgerydescription
Background: Previous studies have examined the role of APOE variation in multiple sclerosis (MS), but have lacked the statistical power to detect modest genetic influences on risk and disease severity. The meta- and pooled analyses presented here utilize the largest collection, to date, of MS cases, controls, and families genotyped for the APOE epsilon polymorphism. Methods: Studies of MS and APOE were identified by searches of PubMed, Biosis, Web of Science, Cochrane Review, and Embase. When possible, authors were contacted for individual genotype data. Meta-analyses of MS case-control data and family-based analyses were performed to assess the association of APOE epsilon genotype with disease risk. Pooled analyses of MS cases were also performed to assess the influence of APOE epsilon genotype on disease severity. Results: A total of 22 studies (3,299 MS cases and 2,532 controls) were available for meta-analysis. No effect of e2 or e4 status on MS risk was observed (summary OR 1.14, 95% CI 0.96–1.34 and OR 0.89, 95% CI 0.78–1.01). Results obtained from analyses of APOE genotypes in 1,279 MS families were also negative ( p = 0.61). Finally, results from pooled analyses of 4,048 MS cases also argue strongly that APOE epsilon status does not distinguish a relapsing-remitting from primary progressive disease course, or influence disease severity, as measured by the Expanded Disability Status Scale and disease duration. Conclusion: Overall, these findings do not support a role for APOE in multiple sclerosis, and underscore the importance of using large sample sizes to detect modest genetic effects, particularly in studies of genotype-phenotype relationships.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2006-05-09 |