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Vol. 25, No. 4, 2008
Issue release date: April 2008

Analysis of UBQLN1 Variants in a Polish Alzheimer’s Disease Patient: Control Series

Golan M.P. · Melquist S. · Safranow K. · Styczyńska M. · Słowik A. · Kobryś M. · Żekanowski C. · Barcikowska M.
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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.

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