Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alzheimer's disease (AD) is a genetically complex and heterogeneous disorder. To date, a large number of candidate genes have been associated with the disease, however none of these findings has been consistently replicated in independent datasets. In this study we report the results of family-based analyses for polymorphisms of five such candidates on chromosomes 2 (interleukin-1beta, IL-1B), 3 (butyrylcholinesterase, BCHE), 11 (cathepsin D, CTSD; Fe65, APBB1) and 12 (lipoprotein receptor-related protein-1, LRP1) that were all suggested to be associated with AD in recent case-control studies. To minimize the possibility of spurious findings due to population admixture, we used a family-based design applying the sibship disequilibrium test (SDT) as well as two-point parametric linkage analyses on families from the National Institute of Mental Health (NIMH) Genetics Initiative. Contrary to the initial reports, none of the polymorphisms that were analyzed showed evidence for association or linkage with AD in our families. Our results suggest that the previously reported associations from case-control studies are either (a) false positive results, e.g. due to type I error or population admixture, (b) smaller than initially proposed, or (c) due to linkage disequilibrium with an as yet unidentified polymorphism nearby.
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PMID:Candidate genes showing no evidence for association or linkage with Alzheimer's disease using family-based methodologies. 1111 13

There is considerable enthusiasm for the prospect of using common polymorphisms (primarily single nucleotide polymorphisms; SNPs) in candidate genes to unravel the genetics of complex disease. This approach has generated a number of findings of loci which are significantly associated with sporadic Alzheimer's disease (AD). In the present study, a total of 15 genes of interest were chosen from among the previously published reports of significant association in AD. Genotyping was performed on polymorphisms within those genes (14 SNPs and one deletion) using Dynamic Allele Specific Hybridization (DASH) in 204 Swedish patients with sporadic late-onset AD and 186 Swedish control subjects. The genes chosen for analysis were; low-density lipoprotein receptor-related protein (LRP1), angiotensin converting enzyme (DCP1), alpha-2-macroglobulin (A2M), bleomycin hydrolase (BLMH), dihydrolipoyl S-succinyltransferase (DLST), tumour necrosis factor receptor superfamily member 6 (TNFRSF6), nitric oxide synthase (NOS3), presenilin 1 (PSEN1), presenilin 2 (PSEN2), butyrylcholinesterase (BCHE), Fe65 (APBB1), oestrogen receptor alpha (ESR1), cathepsin D (CTSD), methylenetetrahydrofolate reductase (MTHFR), and interleukin 1A (IL1A). We found no strong evidence of association for any of these loci with AD in this population. While the possibility exists that the genes analysed are involved in AD (ie they have weak effects and/or are population specific), results reinforce the need for extensive replication studies if we are to be successful in defining true risk factors in complex diseases.
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PMID:Lack of replication of association findings in complex disease: an analysis of 15 polymorphisms in prior candidate genes for sporadic Alzheimer's disease. 1143 25

The aim of our work was to detect minor loci acting as Alzheimer's disease (AD) genetic markers. We divided 206 AD patients and 186 individuals as controls into six age at onset/age-dependent groups. We studied polymorphisms of the genes of apolipoprotein E (APOE) and its promoter, cathepsin D, butyrylcholinesterase, cystatin C, methionine synthase, and cystathionine beta-synthase. Our results demonstrated that data analysis according to age at onset allows the detection of minor genetic risk factors for AD. Thus, the Th1/E47cs-G allele was an independent AD risk factor after 80 years, whereas the catD-T, BChE-K, CBS-844ins68, and CBS-VNTR 19 alleles are independent AD risk factors after 75 years. On the other hand, the CST3-A allele was an independent AD risk factor before 60 years while the CBS-VNTR allele 21 was an independent AD risk factor before 64 years. In contrast, the MS-AA genotype was an AD risk factor unrelated to age at onset. In conclusion, two main tasks remain to be accomplished to facilitate early detection of people at risk of developing AD: (1) the establishment of common criteria to carry out association studies for different genetic markers, including the introduction of AD age at onset as a crucial variable in each study, and (2) the definition of global and population-specific genetic markers for each age at onset AD subgroup.
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PMID:Age at onset: an essential variable for the definition of genetic risk factors for sporadic Alzheimer's disease. 1639