title: APOE and APOC1 promoter polymorphisms and the risk of Alzheimer disease in African American and Caribbean Hispanic individuals.
abstract: BACKGROUND
  The APOE epsilon4 allele is a genetic risk factor for Alzheimer disease (AD), though the strength of the association varies by ethnic group. Polymorphisms in regulatory sequences of APOE have also been related to AD, but the effects are inconsistent across studies.
  
  
  METHODS
  We examined the association between AD and variants in 3 APOE promoters and in the promoter of the adjacent APOC1 gene in African American and Caribbean Hispanic individuals. Polymorphisms tested were the -491A/T, -427T/C, and -219G/T (Th1/E47cs) in the APOE promoter and the HpaI variant in the APOC1 promoter. Using standard research criteria for AD, overall odds ratios were computed and repeated stratified by presence or absence of APOE epsilon4.
  
  
  RESULTS
  The APOC1 HpaI+ variant was associated with AD in Caribbean Hispanic individuals, but strong linkage disequilibrium with the APOE epsilon4 allele indicated that this was not an independent effect. No promoter variant in APOE or APOC1 was associated with AD before or after adjusting for age, education, sex, and multiple comparisons. Estimated haplotypes including -219G/T, APOE, and APOC1 differed significantly in Caribbean Hispanic patients and controls but not in African American participants. This effect was primarily owing to the -219G/T-APOE haplotype, but we did not detect significant allele-specific differences in promoter activity comparing reporter constructs containing the APOE -219G and -219 T alleles.
  
  
  CONCLUSIONS
  These findings exclude a strong or independent influence of APOE or APOC1 promoter polymorphisms on the variation in APOE-related risk of AD in African American and Caribbean Hispanic individuals.
authors.affiliation: Department of Pathology, Division of Neuropathology, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Tycko
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Lee
authors.forename: Alejandra
authors.initials: A
authors.lastname: Ciappa
authors.forename: Anjana
authors.initials: A
authors.lastname: Saxena
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Feng
authors.forename: Alex
authors.initials: A
authors.lastname: Arriaga
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Stern
authors.forename: Rafael
authors.initials: R
authors.lastname: Lantigua
authors.forename: Neil
authors.initials: N
authors.lastname: Shachter
authors.forename: Richard
authors.initials: R
authors.lastname: Mayeux
mesh_terms: D001741:Black or African American / Q000208:ethnology; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000208:ethnology* / Q000235:genetics*; D053327:Apolipoprotein E4; D001056:Apolipoproteins C / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D017691:Caribbean Region / Q000208:ethnology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006630:Hispanic or Latino / Q000208:ethnology; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4; D001056:Apolipoproteins C; D001057:Apolipoproteins E