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Association study of cathepsin D gene polymorphism in Iranian patients with sporadic late-onset Alzheimer's disease.
Dement Geriatr Cogn Disord 2014; 37(5-6):257-64DG

Abstract

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.

Authors+Show Affiliations

Department of Medical Genetics, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24281128

Citation

Sayad, Azadeh, et al. "Association Study of Cathepsin D Gene Polymorphism in Iranian Patients With Sporadic Late-onset Alzheimer's Disease." Dementia and Geriatric Cognitive Disorders, vol. 37, no. 5-6, 2014, pp. 257-64.
Sayad A, Noruzinia M, Zamani M, et al. Association study of cathepsin D gene polymorphism in Iranian patients with sporadic late-onset Alzheimer's disease. Dement Geriatr Cogn Disord. 2014;37(5-6):257-64.
Sayad, A., Noruzinia, M., Zamani, M., Harirchian, M. H., & Kazemnejad, A. (2014). Association study of cathepsin D gene polymorphism in Iranian patients with sporadic late-onset Alzheimer's disease. Dementia and Geriatric Cognitive Disorders, 37(5-6), pp. 257-64. doi:10.1159/000347128.
Sayad A, et al. Association Study of Cathepsin D Gene Polymorphism in Iranian Patients With Sporadic Late-onset Alzheimer's Disease. Dement Geriatr Cogn Disord. 2014;37(5-6):257-64. PubMed PMID: 24281128.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association study of cathepsin D gene polymorphism in Iranian patients with sporadic late-onset Alzheimer's disease. AU - Sayad,Azadeh, AU - Noruzinia,Mehrdad, AU - Zamani,Mahdi, AU - Harirchian,Mohammad Hossein, AU - Kazemnejad,Anoushiravan, Y1 - 2013/11/23/ PY - 2013/01/03/accepted PY - 2013/11/28/entrez PY - 2013/11/28/pubmed PY - 2015/2/3/medline SP - 257 EP - 64 JF - Dementia and geriatric cognitive disorders JO - Dement Geriatr Cogn Disord VL - 37 IS - 5-6 N2 - 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. SN - 1421-9824 UR - https://www.unboundmedicine.com/medline/citation/24281128/Association_study_of_cathepsin_D_gene_polymorphism_in_Iranian_patients_with_sporadic_late_onset_Alzheimer's_disease_ L2 - https://www.karger.com?DOI=10.1159/000347128 DB - PRIME DP - Unbound Medicine ER -