Details

Autor(en) / Beteiligte

• Owen, Michael J
• Kehoe, Patrick G
• Russ, Carsten
• McIlroy, Stephen
• Williams, Hywel
• Holmans, Peter
• Holmes, Clive
• Liolitsa, Danae
• Vahidassr, Djamil
• Powell, John
• McGleenon, Bronagh
• Liddell, Malcolm
• Plomin, Robert
• Dynan, Kevin
• Williams, Nigel
• Neal, Jim
• Cairns, Nigel J
• Wilcock, Gordon
• Passmore, Peter
• Lovestone, Simon
• Williams, Julie

Titel

Variation in DCP1 , encoding ACE, is associated with susceptibility to Alzheimer disease

Ist Teil von

• Nature genetics, 1999-01, Vol.21 (1), p.71-72

Ort / Verlag

United States

Erscheinungsjahr

1999

Quelle

MEDLINE

Beschreibungen/Notizen

• The member of 4 allele of the gene encoding apolipoprotein E (APOE) is the only well-replicated genetic risk factor for non-autosomal dominant forms of Alzheimer disease (AD). However, the APOE genotype is estimated to account for less than one-half of the genetic variance. Following reports that the DCP1*D allele of a common insertion (I)/deletion (D) polymorphism in the gene encoding angiotensin converting enzyme (dipeptidyl carboxypeptidase 1; DCP1) is associated with increased longevity, we hypothesized that DCP1*D might protect against the development of AD and that, similarly, the DCP1*I allele may confer increased risk. We tested this hypothesis in a case-control sample from Cardiff and independent replication samples from London and Belfast. Our analysis of the Cardiff data showed a significant association between AD and DCP1 genotypes ( chi super(2)=8.98, d.f.=2, P=0.011) and alleles ( chi super(2)=5.34, d.f.=1, P=0.02). The variance in genotypic distribution appeared attributable to an excess of DCP1*I/*I and DCP1*I/*D genotypes in AD cases (P=0.006; odds ratio (OR)=2.43, 95% CI=1.35-4.39, after Bonferroni correction for multiple testing in the present study; P=0.046 after correction for 8 genes studied previously in this sample). We subsequently tested this finding in the London and Belfast samples and found similar significant associations (London, P=0.0008, OR=2.71, 95% CI=1.5-4.9; Belfast, P=0.017, OR=1.82, 95% CI=1.11-2.98). We combined the samples in a stratified analysis, and found that AD cases had a highly significant excess of DCP1*I/*I and DCP1*I/*D genotypes (n=542) compared with controls (n=386; chi super(2)=24.22, d.f.=1, P=0.000001). This yielded an OR of 2.22 (95% CI=1.62-3.1) with no evidence of heterogeneity between samples (P=0.6).