These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: The apolipoprotein E/CI/CII gene cluster and late-onset Alzheimer disease.
    Author: Yu CE, Payami H, Olson JM, Boehnke M, Wijsman EM, Orr HT, Kukull WA, Goddard KA, Nemens E, White JA.
    Journal: Am J Hum Genet; 1994 Apr; 54(4):631-42. PubMed ID: 8128960.
    Abstract:
    The chromosome 19 apolipoprotein E/CI/CII gene cluster was examined for evidence of linkage to a familial Alzheimer disease (FAD) locus. The family groups studied were Volga German (VG), early-onset non-VG (ENVG; mean age at onset < 60 years), and late-onset families. A genetic association was observed between apolipoprotein E (ApoE) allele epsilon 4 and FAD in late-onset families; the epsilon 4 allele frequency was .51 in affected subjects, .37 in at-risk subjects, .11 in spouses, and .19 in unrelated controls. The differences between the epsilon 4 frequencies in affected subjects versus controls and in at-risk subjects versus controls were highly significant (standard normal deviate [ZSND]) = 7.37, P < 10(-9); and ZSND = 4.07, P < .00005, respectively). No association between the epsilon 4 allele and FAD was observed in the ENVG or VG groups. A statistically significant allelic association between epsilon 4 and AD was also observed in a group of unrelated subjects; the epsilon 4 frequency was .26 in affected subjects, versus .19 in controls (ZSND = 2.20, P < .03). Evidence of linkage of ApoE and ApoCII to FAD was examined by maximum-likelihood methods, using three models and assuming autosomal dominant inheritance: (1) age-dependent penetrance, (2) extremely low (1%) penetrance, and (3) age-dependent penetrance corrected for sporadic Alzheimer disease (AD). For ApoCII in late-onset families, results for close linkage were negative, and only small positive lod-score-statistic (Z) values were obtained (model 1, maximum Z[Zmax] = 0.61, recombination fraction [theta] = .30; model 2, Zmax = 0.47, theta = .20). For ApoE in late-onset kindreds, positive Z values were obtained when either allele frequencies from controls (model 1, Zmax = 2.02, theta = .15; model 2, Zmax = 3.42, theta = .05) or allele frequencies from the families (model 1, Zmax = 1.43, theta = .15; model 2, Zmax = 1.70, theta = .05) were used. When linkage disequilibrium was incorporated into the analysis, the Z values increased (model 1, Zmax = 3.17, theta = .23; model 3, Zmax = 1.85, theta = .20). For the ENVG group, results for ApoE and ApoCII were uniformly negative. Affected-pedigree-member analysis gave significant results for the late-onset kindreds, for ApoE (ZSND = 3.003, P = .003) and ApoCII (ZSND = 2.319, P = .016), when control allele frequencies were used but not when allele frequencies were derived from the families.
    [Abstract] [Full Text] [Related] [New Search]