Cathepsin D gene exon 2 polymorphism and sporadic Alzheimer's disease

McIlroy, Stephen P.; Dynan, Kevin B.; McGleenon, B M; Lawson, John T.; Passmore, Anthony Peter

doi:10.1016/s0304-3940(99)00635-7

Cited by 33 publications

(21 citation statements)

References 13 publications

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“…An association between Ala224Val polymorphism and AD has already been reported by Papassotiropoulos et al [17,18] in 2 German populations in 1999 and 2000, respectively, with 13.6 and 9.8% T-carrying-genotype frequency in controls, which was close to our finding in Iran (14%). But this association has not been reproduced in other studies [19,20,21,36,37]. Except in a recent case-control study on 219 patients with AD and 215 controls, Albayrak et al [38] showed that a significantly higher proportion of T allele carriers exists among male AD patients (28.5%) when compared with male controls (13.8%) (p = 0.013).…”

Section: Discussionmentioning

confidence: 93%

Association Study of Cathepsin D Gene Polymorphism in Iranian Patients with Sporadic Late-Onset Alzheimer's Disease

Sayad¹,

Noruzinia²,

Zamani³

et al. 2013

Dement Geriatr Cogn Disord

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One of the most prevalent forms of dementia is Alzheimer's disease (AD). Complex inheritance and multifactorial patterns of late-onset AD (LOAD) along with its heterogeneity are due to the presence of different AD-predisposing genes with different influence on disease development among various populations. A key event in the pathogenesis of AD is the deposition of β-amyloid peptide, which is derived from the amyloid precursor protein by β- and γ-secretases. Cathepsin D (CTSD) is an acid protease with β- and γ-secretase-like features in vitro. An exonic C→T polymorphism at position 224 of the CTSD gene (rs: 17571) has been shown to be associated with the enzyme function of CTSD and with AD. Two studies in the German population reported a strong association of this polymorphism with an increased risk of developing AD, while other studies did not confirm this observation. We tested for this association in a case-control study in 100 Iranian sporadic LOAD patients based on diagnostic criteria of DSM-IV-TR and NINCDS-ADRDA and in 100 normal controls without any personal and family history of AD or other related dementias. Polymerase chain reaction-restriction fragment length polymorphism was set up to detect this polymorphism. Our study demonstrated that T-carrying genotype frequency in AD patients is significantly higher than in controls and there was a 2.5-fold increased risk for developing AD in the T-carrying genotype compared to C/C genotype (odds ratio = 2.5, p = 0.010). The odds ratio for subjects with the apolipoprotein E ε4 (APOE ε4) allele was 2.91 (p = 0.003) and carriers of the CTSD T and APOE ε4 alleles had a 6.25-fold increased risk of the disease (p = 0.0). Our results indicate that CTSD genotype is associated with the disease and a combination of the above risk factors significantly alters the risk for developing AD.

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Section: Discussionmentioning

confidence: 93%

Association Study of Cathepsin D Gene Polymorphism in Iranian Patients with Sporadic Late-Onset Alzheimer's Disease

Sayad¹,

Noruzinia²,

Zamani³

et al. 2013

Dement Geriatr Cogn Disord

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“…[9][10][11][12][13][14] However, three case-control studies that reported a negative association in Caucasians did observe a nonsignificant increase in T allele frequency in AD cases compared to controls. [11][12][13] The fourth negative case-control study showed a nonsignificant increase in younger AD patients carrying the T allele. 14 As intelligence is a risk factor for the onset of dementia we propose that the above age-matched case-control studies were detecting an association between intelligence and disease onset.…”

Section: Discussionmentioning

confidence: 97%

“…A functional polymorphism (C4T, Ala4Val) within exon 2 of the CTSD gene increases the secretion of pro-CTSD from the cell 8 and has also been reported as a risk factor in AD, although this finding has been challenged. [9][10][11][12][13][14][15] A role for CTSD in apoptosis has also been established, 16,17 and its importance in brain development has recently been highlighted owing to its involvement in congenital ovine neuronal lipofuscinosis. 18 …”

Section: Introductionmentioning

confidence: 99%

Cathepsin D exon 2 polymorphism associated with general intelligence in a healthy older population

et al. 2003

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General intelligence is a heritable trait that is a risk factor for both the onset of dementia and the rate of cognitive decline in community-dwelling older persons. Previous studies screening for quantitative trait loci (QTLs) that influence general intelligence in healthy individuals have identified four loci, two of which are located within the genes insulin-like growth factor 2 receptor (IGF2R) and the Msx1 homeobox. Here, we report the finding of another QTL associated with general intelligence that is located within exon 2 of the cathepsin D (CTSD) gene. A group of 767 healthy adults with a follow-up period of over 15 years have been analyzed for cross-sectional and longitudinal trends in cognitive change using the Heim intelligence test score (AH4-1). We observed a significant association (P ¼ 0.01) between a functional C4T (Ala4Val) transition within exon 2 of the CTSD gene that increases the secretion of pro-CTSD from the cell, and the AH4-1 score at initial testing on entry to the longitudinal study. Interestingly, CTSD is transported by IGF2R from the trans Golgi network to the lysosome.

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“…An increased representation of the CTSD T* allele has been associated with a higher risk of AD [19,20] while other studies found a small increase in the risk [25] or did not confirm this finding [26][27][28][29].…”

Section: Introductionmentioning

confidence: 87%

Cathepsin D Polymorphism in Italian Elderly Subjects with Sporadic Late-Onset Alzheimer’s Disease

Ingegni¹,

Nocentini

Mariani³

et al. 2003

Dement Geriatr Cogn Disord

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Alzheimer’s disease (AD) is the most frequent cause of dementia in elderly people. Different pathological pathways have been involved in the development of late-onset AD. Among them, numerous genes have been proposed as pathogenetic factors acting independently or interactively. It has been suggested that the cathepsin D gene (CTSD) is associated with late-onset AD. We analyzed an exonic polymorphism of the CTSD gene [C→T (Ala→Val) transition at position 224] in 142 AD patients and 120 controls. Our data indicate no significant association between this polymorphism and the risk of AD. Likewise there was no association between CTSD polymorphism and the apolipoprotein E genotype in the risk of developing AD.

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Cathepsin D gene exon 2 polymorphism and sporadic Alzheimer's disease

Cited by 33 publications

References 13 publications

Association Study of Cathepsin D Gene Polymorphism in Iranian Patients with Sporadic Late-Onset Alzheimer's Disease

Association Study of Cathepsin D Gene Polymorphism in Iranian Patients with Sporadic Late-Onset Alzheimer's Disease

Cathepsin D exon 2 polymorphism associated with general intelligence in a healthy older population

Cathepsin D Polymorphism in Italian Elderly Subjects with Sporadic Late-Onset Alzheimer’s Disease

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