| dc.description.abstract | Dementia and depression are important causes of dependence and disability among the elderly, with severe consequences for the family and health care system. Study of biomarkers is essential to understand pathophysiology of the disease, early diagnosis and search of new therapeutic targets. The aim of this study was to detect any association between polymorphisms of the Clusterin (CLU) and the Complement Receptor 1 (CR1) genes and AD or depression in Brazilian elderly. It was a cross-section case-control study, with 501 individuals over 60 years, divided in three groups: 211 late-onset Alzheimer's disease (LOAD) patients (women 135; mean age 80 years), 182 major depression individuals (women 148; mean age 76 years) and 108 control subjects (women 75; mean age 78 years). The mean score at MMSE test was 13 points (Alzheimer's disease), 23 points (depression) and 26 points (Control). All analyzed polymorphisms satisfied the Hardy-Weinberg equilibrium (HWE). Two common genetic variants (rs 2279590 and rs9331888) in the CLU gene and one (rs 6656401) in CR1 gene were genotyped using TaqMan® technology. The ancestral allele (C) and the genotype (C/C) of the rs2279590 polymorphism within CLU were significantly associated with an increased risk of LOAD (OR = 1,52; p = 0.01 and OR = 2; p = 0.02, respectively). Haplotype analysis identified a risk haplotype (C/C) (OR= 1.23, p = 0.02) and a protective haplotype (C-T) (OR 0.77, p = 0.03). However, after adjustment, such associations were not maintained, possibly, due to the sample size or ethnic difference, as no other similar study in Brazilian population was published until now. No association between polimorphism of the CR1 gene were found for LOAD or major depression in our sample. These findings suggest CLU as a susceptibility gene for LOAD in a sample of Brazilian population. Larger genetic studies would be needed in the future, to further investigate those genes function and to clarify their functional roles in Alzheimers disease. | |
