期刊
AMERICAN JOURNAL OF HUMAN GENETICS
卷 70, 期 3, 页码 708-717出版社
CELL PRESS
DOI: 10.1086/339269
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资金
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS026799, R01NS032830] Funding Source: NIH RePORTER
- NINDS NIH HHS [NS32830, NS26799, R01 NS026799, R01 NS032830] Funding Source: Medline
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).
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