title: Association of polymorphisms in the apolipoprotein E region with susceptibility to and progression of multiple sclerosis.
abstract: Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, with a complex etiology that includes a strong genetic component. The contribution of the major histocompatibility complex (MHC) has been established in numerous genetic linkage and association studies. In addition to the MHC, the chromosome 19q13 region surrounding the apolipoprotein E (APOE) gene has shown consistent evidence of involvement in MS when family-based analyses were conducted. Furthermore, several clinical reports have suggested that the APOE-4 allele may be associated with more-severe disease and faster progression of disability. To thoroughly examine the role of APOE in MS, we genotyped its functional alleles, as well as seven single-nucleotide polymorphisms (SNPs) located primarily within 13 kb of APOE, in a data set of 398 families. Using family-based association analysis, we found statistically significant evidence that an SNP haplotype near APOE is associated with MS susceptibility (P=.005). An analysis of disease progression in 614 patients with MS from 379 families indicated that APOE-4 carriers are more likely to be affected with severe disease (P=.03), whereas a higher proportion of APOE-2 carriers exhibit a mild disease course (P=.02).
authors.affiliation: Center for Human Genetics, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Silke
authors.initials: S
authors.lastname: Schmidt
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Barcellos
authors.forename: Karen
authors.initials: K
authors.lastname: DeSombre
authors.forename: Jacqueline B
authors.initials: JB
authors.lastname: Rimmler
authors.forename: Robin R
authors.initials: RR
authors.lastname: Lincoln
authors.forename: Patricia
authors.initials: P
authors.lastname: Bucher
authors.forename: Ann M
authors.initials: AM
authors.lastname: Saunders
authors.forename: Eric
authors.initials: E
authors.lastname: Lai
authors.forename: Eden R
authors.initials: ER
authors.lastname: Martin
authors.forename: Jeffery M
authors.initials: JM
authors.lastname: Vance
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Oksenberg
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hauser
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics*; D002648:Child; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011336:Probability; D016019:Survival Analysis
chemical_list: D001057:Apolipoproteins E