title: Analysis of UBQLN1 variants in a Polish Alzheimer's disease patient: control series.
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.
authors.affiliation: Department of Neurodegenerative Disorders, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland. maciekg@cmdik.pan.pl
authors.forename: Maciej P
authors.initials: MP
authors.lastname: Golan
authors.forename: Stacey
authors.initials: S
authors.lastname: Melquist
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Safranow
authors.forename: Maria
authors.initials: M
authors.lastname: Styczyńska
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Słowik
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Kobryś
authors.forename: Cezary
authors.initials: C
authors.lastname: Zekanowski
authors.forename: Maria
authors.initials: M
authors.lastname: Barcikowska
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006239:Haplotypes; D006801:Humans; D008297:Male; D011044:Poland / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D053327:Apolipoprotein E4; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C107792:UBQLN1 protein, human