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Genetic association of argyrophilic grain disease with polymorphisms in alpha‐2 macroglobulin and low‐density lipoprotein receptor‐related protein genes
Author(s) -
Ghebremedhin E.,
Schultz C.,
Thal D. R.,
Del Tredici K.,
Rueb U.,
Braak H.
Publication year - 2002
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1046/j.1365-2990.2002.00398.x
Subject(s) - apolipoprotein e , allele , genotype , polymorphism (computer science) , biology , allele frequency , alzheimer's disease , ldl receptor , endocrinology , medicine , macroglobulin , valine , genetics , gene , lipoprotein , cholesterol , microbiology and biotechnology , disease , amino acid
Argyrophilic grain disease (AGD) is a neurodegenerative disorder of the aged human brain associated with the formation of abnormal tau protein in specific neurones and macroglial cells. Previously, we reported the association between AGD and the ε2 allele of apolipoprotein E (ApoE). Here, the polymorphisms of the alpha‐2 macroglobulin gene (A2M) and those of the low‐density lipoprotein receptor‐related protein gene (LRP) were assessed in 115 AGD cases and compared with 170 controls. The results reveal an association between AGD and the C766T polymorphism of LRP ( P =0.001). In addition, the present study shows that the valine to isoleucine (Val1000Ile) polymorphism of A2M is linked with AGD ( P =0.03). By comparison, no relationship between AGD and the intronic 5‐bp deletion/insertion polymorphism of A2M is demonstrable ( P =0.8). Finally, this report corroborates and extends our earlier finding in that the frequency of the ε2 allele of ApoE is higher in AGD cases than in controls (17.4% vs. 8.5%, P =0.003), whereas the ε4 allele frequency approximates that in control cases (13.9% vs. 13.2%, P =0.93). This association, however, is only apparent in the presence of the LRP CC genotype. In conclusion, the present study shows that AGD is associated with the LRP, A2M and ApoE genes.