Dataset Information

Does APOE explain the linkage of Alzheimer's disease to chromosome 19q13?

ABSTRACT: We have studied the impact of the apolipoprotein E gene (APOE) on the chromosome 19 linkage peak from an analysis of sib-pairs affected by Alzheimer's disease. We genotyped 417 affected sib-pairs (ASPs) collected in Sweden and Norway (SWE), the UK and the USA for 10 microsatellite markers on chromosome 19. The highest Zlr (3.28, chromosome-wide P-value 0.036) from the multipoint linkage analysis was located approximately 1 Mb from APOE, at marker D19S178. The linkage to chromosome 19 was well explained by APOE in the whole sample as well as in the UK and USA subsamples, as identity by descent (IBD) increased with the number of epsilon4 alleles in ASPs. There was a suggestion from the SWE subsample that linkage was higher than would be expected from APOE alone, although the test for this did not reach formal statistical significance. There was also a significant age at onset (aao) effect on linkage to chromosome 19q13 in the whole sample, which manifested itself as increased IBD sharing in relative pairs with lower mean aao. This effect was partially, although not completely, explained by APOE. The aao effect varied considerably between the different subsamples, with most of the effect coming from the UK sample. The other samples showed smaller effects in the same direction, but these were not significant.

SUBMITTER: Blom ES

PROVIDER: S-EPMC2726752 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Does APOE explain the linkage of Alzheimer's disease to chromosome 19q13?

Blom Elin S ES Holmans Peter P Arepalli Sampath S Adighibe Omanma O Hamshere Marian L ML Gatz Margaret M Pedersen Nancy L NL Bergem A L Mina AL Owen Michael J MJ Hollingworth Paul P Goate Alison A Williams Julie J Lannfelt Lars L Hardy John J Wavrant-De Vrièze Fabienne F Glaser Anna A

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 20080901 6

We have studied the impact of the apolipoprotein E gene (APOE) on the chromosome 19 linkage peak from an analysis of sib-pairs affected by Alzheimer's disease. We genotyped 417 affected sib-pairs (ASPs) collected in Sweden and Norway (SWE), the UK and the USA for 10 microsatellite markers on chromosome 19. The highest Zlr (3.28, chromosome-wide P-value 0.036) from the multipoint linkage analysis was located approximately 1 Mb from APOE, at marker D19S178. The linkage to chromosome 19 was well ex ...[more]

PMID: 18161859

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Project description:The apolipoprotein E (APOE) and tau proteins play important roles in the pathological development of Alzheimer's disease (AD). Many studies have shown an association between the APOE gene and AD. Association between AD and the newly discovered saitohin (STH) gene, nested within the intron of the tau gene, has been reported. The present study aimed to elucidate the association between APOE and AD, and between STH and AD in our sample.The functional polymorphisms, rs429358 and rs7412, in the APOE gene (which together define the epsilon2, epsilon3, and epsilon4 alleles), and the Q7R SNP in the STH gene, were genotyped in 369 patients with AD and 289 healthy European-Americans. The associations between these two genes and AD were analyzed in a case-control design.Consistent with previously reported results, the frequencies of the APOE epsilon4 allele, epsilon4/epsilon4 genotype and epsilon3/epsilon4 genotype were significantly higher in AD cases than controls; the epsilon4/epsilon4 genotype frequency was significantly higher in early-onset AD (EOAD) than late-onset AD (LOAD); the frequencies of the epsilon2 allele, epsilon3 allele, epsilon3/epsilon3 genotype and epsilon2/epsilon3 genotype were significantly lower in AD cases than controls. Positive likelihood ratios (LRs+) of APOE alleles and genotypes increased in a linear trend with the number of epsilon4 alleles and decreased in a linear trend with the number of epsilon2 or epsilon3 alleles. There was no significant difference in the STH allele and genotype frequency distributions between AD cases and controls.This study confirmed that the epsilon4 allele is a dose-response risk factor for AD and the epsilon4/epsilon4 genotype was associated with a significantly earlier age of onset. Moreover, we found that the epsilon2 allele was a dose-response protective factor for AD and the epsilon3 allele exerted a weaker dose-response protective effect for risk of AD compared with epsilon2. In a clinical setting, APOE genotyping could offer additional biological evidence of whether a subject may develop AD, but it is not robust enough to serve as an independent screening or predictive test in the diagnosis of AD. STH variation was not significantly associated with AD in our sample.

Dataset Information

Does APOE explain the linkage of Alzheimer's disease to chromosome 19q13?

Publications

Does APOE explain the linkage of Alzheimer's disease to chromosome 19q13?

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