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

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 beta-amyloid peptide, which is derived from the amyloid precursor protein by beta-and gamma-secretases. Cathepsin D (CTSD) is an acid protease with beta-and gamma-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 DSMIV-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 epsilon 4 (APOE epsilon 4) allele was 2.91 (p = 0.003) and carriers of the CTSD T and APOE epsilon 4 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. Copyright (C) 2013 S. Karger AG, Basel