Publications (4)8.98 Total impact
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Article: Analysis of UBQLN1 variants in a Polish Alzheimer's disease patient: control series.
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ABSTRACT: Late-onset Alzheimer's disease (LOAD) is the most common neurodegenerative disorder, and has a complex etiology. Recently an intronic polymorphism in the ubiquilin 1 gene (UBQLN1) and a particular haplotype was reported to be associated with LOAD. We investigated whether variants in UBQLN1 confer a risk for the disease in 407 Polish LOAD patients and 407 controls. We observed a weak association with the rs2781002 polymorphism, however, contrary to the initial reports, in our group the association was with the A allele. Risk estimation for AA versus GG genotypes showed that the AA genotype is a weak risk factor for AD (OR = 1.8, 95% CI = 1.1-3.1, p = 0.025). This effect was stronger in a group of LOAD patients without APOE4 allele. Haplotype analyses indicate that there is an increase of haplotypes with an A allele in the case group. Also, the specific haplotypes with the A allele that increase AD risk differ between the APOE4-positive and APOE4-negative pools. However, the association observed seems to be driven mostly by rare (<5%) haplotypes. Results suggest a need for additional association studies and in silico analysis of the UBQLN1 locus.Dementia and Geriatric Cognitive Disorders 01/2008; 25(4):366-71. · 2.14 Impact Factor -
Article: Sigma receptor type 1 gene variation in a group of Polish patients with Alzheimer's disease and mild cognitive impairment.
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ABSTRACT: The sigma-1 receptor (SIGMAR1) is a subtype of a nonopioid sigma receptor family and is implicated in numerous functions connected with Alzheimer's disease (AD). Two common genetic variants were identified in SIGMAR1: GC-241 -240TT and Q2P (A61C). It was suggested that the TT-C haplotype is a protective factor for AD. We decided to investigate a putative link between the variants of SIGMAR1 and AD in a group of Polish patients with late-onset AD, in patients with mild cognitive impairment, and in a control group. We observed no significant differences for the SIGMAR1 allele, genotype, haplotype, and diplotype distributions between the studied groups. Multivariate logistic regression analysis showed no interaction between the APOE4 and SIGMAR1 polymorphisms. Further studies using data from different populations are required to elucidate the effect of SIGMAR1 polymorphisms on AD.Dementia and Geriatric Cognitive Disorders 02/2007; 23(6):432-8. · 2.14 Impact Factor -
Article: Two novel presenilin 1 gene mutations connected with frontotemporal dementia-like clinical phenotype: genetic and bioinformatic assessment.
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ABSTRACT: Mutations in the amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) genes are associated with early-onset familial Alzheimer's disease (EOAD). There are several reports describing mutations in PSEN1 in cases with frontotemporal dementia (FTD). We identified two novel mutations in the PSEN1 gene: L226F and L424H. The first mutation was detected in a patient with a clinical diagnosis of FTD and a post-mortem diagnosis of AD. The second mutation is connected with a clinical phenotype of variant AD with strong FTD signs. In silico modeling revealed that the mutations, as well as mutations used for comparison (F177L and L424R), change the local structure, stability and/or properties of the transmembrane regions of the presenilin 1 protein (PS1). In contrast, a silent non-synonymous substitution F175S is eclipsed by external residues and has no influence on PS1 interfacial surface. We suggest that in silico analysis of PS1 substitutions can be used to characterize novel PSEN1 mutations, to discriminate between silent polymorphisms and a potential disease-causing mutation. We also propose that PSEN1 mutations should be considered in FTD patients with no MAPT mutations.Experimental Neurology 08/2006; 200(1):82-8. · 4.70 Impact Factor -
Article: Two novel presenilin 1 gene mutations connected with frontotemporal dementia-like clinical phenotype: Genetic and bioinformatic assessment
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ABSTRACT: Mutations in the amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) genes are associated with early-onset familial Alzheimer's disease (EOAD). There are several reports describing mutations in PSEN1 in cases with frontotemporal dementia (FTD). We identified two novel mutations in the PSEN1 gene: L226F and L424H. The first mutation was detected in a patient with a clinical diagnosis of FTD and a post-mortem diagnosis of AD. The second mutation is connected with a clinical phenotype of variant AD with strong FTD signs.In silico modeling revealed that the mutations, as well as mutations used for comparison (F177L and L424R), change the local structure, stability and/or properties of the transmembrane regions of the presenilin 1 protein (PS1). In contrast, a silent non-synonymous substitution F175S is eclipsed by external residues and has no influence on PS1 interfacial surface. We suggest that in silico analysis of PS1 substitutions can be used to characterize novel PSEN1 mutations, to discriminate between silent polymorphisms and a potential disease-causing mutation. We also propose that PSEN1 mutations should be considered in FTD patients with no MAPT mutations.Experimental Neurology.
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2008
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Polish Academy of Sciences
- Zakład Chorob Neurodegeneracyjnych
Warsaw, Masovian Voivodeship, Poland
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