title: Association study of cathepsin D gene polymorphism in Iranian patients with sporadic late-onset Alzheimer's disease.
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.affiliation: Department of Medical Genetics, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Sayad
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Noruzinia
authors.forename: Mahdi
authors.initials: M
authors.lastname: Zamani
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Harirchian
authors.forename: Anoushiravan
authors.initials: A
authors.lastname: Kazemnejad
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D016022:Case-Control Studies; D002402:Cathepsin D / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007492:Iran; D008297:Male; D011110:Polymorphism, Genetic
chemical_list: D053327:Apolipoprotein E4; C533922:CTSD protein, human; D002402:Cathepsin D