OBJECTIVE: To determine whether the effects of APOE promoter polymorphisms on AD are independent of the APOE-epsilon4 allele. BACKGROUND: Recently, the -491 A-->T and -219 G-->T polymorphisms located in the APOE promoter have been suggested to be risk factors for AD. However, the effects of these polymorphisms have not always been reproduced in case-control studies, possibly because of the strong linkage disequilibrium existing at this locus or the characteristics of the populations studied. METHODS: Data collection was performed from six independent samples (1,732 patients with AD and 1,926 control subjects) genotyped for APOE exon 4 and the two APOE promoter polymorphisms. The risks associated with the APOE polymorphisms for developing AD were estimated using logistic regression procedures and calculation of odds ratios with 95% CI adjusted by age, sex, and collection center. Independence of the APOE promoter polymorphisms was tested by stratification for APOE-epsilon4 and tertile design was used for age stratification. RESULTS: The independence of the -491 AA genotype was observed in the whole sample whereas the independence of the -219 TT genotype was observed only in the oldest population. CONCLUSION: The -491 and -219 APOE promoter polymorphisms incur risk for AD in addition to risk associated with the APOE-epsilon4 allele, with age accentuating the effect of the -219 TT genotype. Because these polymorphisms appear to influence apoE levels, these results suggest that APOE expression is an important determinant of AD pathogenesis.
OBJECTIVE: To determine whether the effects of APOE promoter polymorphisms on AD are independent of the APOE-epsilon4 allele. BACKGROUND: Recently, the -491 A-->T and -219 G-->T polymorphisms located in the APOE promoter have been suggested to be risk factors for AD. However, the effects of these polymorphisms have not always been reproduced in case-control studies, possibly because of the strong linkage disequilibrium existing at this locus or the characteristics of the populations studied. METHODS: Data collection was performed from six independent samples (1,732 patients with AD and 1,926 control subjects) genotyped for APOE exon 4 and the two APOE promoter polymorphisms. The risks associated with the APOE polymorphisms for developing AD were estimated using logistic regression procedures and calculation of odds ratios with 95% CI adjusted by age, sex, and collection center. Independence of the APOE promoter polymorphisms was tested by stratification for APOE-epsilon4 and tertile design was used for age stratification. RESULTS: The independence of the -491 AA genotype was observed in the whole sample whereas the independence of the -219 TT genotype was observed only in the oldest population. CONCLUSION: The -491 and -219 APOE promoter polymorphisms incur risk for AD in addition to risk associated with the APOE-epsilon4 allele, with age accentuating the effect of the -219 TT genotype. Because these polymorphisms appear to influence apoE levels, these results suggest that APOE expression is an important determinant of AD pathogenesis.
Authors: Chang-En Yu; Howard Seltman; Elaine R Peskind; Nichole Galloway; Peter X Zhou; Elisabeth Rosenthal; Ellen M Wijsman; Debby W Tsuang; Bernie Devlin; Gerard D Schellenberg Journal: Genomics Date: 2007-04-16 Impact factor: 5.736
Authors: J-C Lambert; D Mann; F Richard; J Tian; J Shi; U Thaker; S Merrot; J Harris; B Frigard; T Iwatsubo; C Lendon; P Amouyel Journal: J Neurol Neurosurg Psychiatry Date: 2005-07 Impact factor: 10.154
Authors: E Arnáiz; O Almkvist; R J Ivnik; E G Tangalos; L O Wahlund; B Winblad; R C Petersen Journal: J Neurol Neurosurg Psychiatry Date: 2004-09 Impact factor: 10.154
Authors: Kristin K Nicodemus; Judith E Stenger; Donald E Schmechel; Kathleen A Welsh-Bohmer; Ann M Saunders; Allen D Roses; John R Gilbert; Jeffery M Vance; Jonathan L Haines; Margaret A Pericak-Vance; Eden R Martin Journal: Neurogenetics Date: 2004-09-29 Impact factor: 2.660