Premium
P3‐263: The kinesin light chain 1 polymorphism rs8702 is associated with elevated CSF levels of secreted forms of amyloid precursor protein
Author(s) -
Palmér Mona Seibt,
Andersson Malin E.,
Minthon Lennart,
Simon Adam J.,
Blennow Kaj,
Zetterberg Henrik
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.1831
Subject(s) - amyloid precursor protein , gene isoform , allele , genotype , kinesin , polymorphism (computer science) , alzheimer's disease , microbiology and biotechnology , protein precursor , gene , medicine , endocrinology , biology , chemistry , disease , biochemistry , genetics , microtubule
phisms with sufficient data available, the website also provides the results of systematic meta-analyses using the published genotype distributions in case-control samples. Methods: In a database freeze on Dec 1st, 2007 a total of 27 loci (ACE, BDNF, CH25H, CHRNB2, CST3, CTSD, DAPK1, GALP, hCG2039140, IL1B, LMNA, LOC439999, LOC651924, MAPT, MTHFR, MYH13, PCK1, PGBD1, PRNP, PSEN1, SORCS1, SORL1, TF, TFAM, TNK1, WGA_14q32.13, WGA_7p15.2) displayed evidence for modest but significant AD risk-effects (average summary odds ratio 1.25), in addition to the established APOE association. In this study we have assessed these genes the majority of which were never tested usingfamily-based methods for association with AD in nearly 4,000 subjects from 1,345 AD families originating from a total of four independent cohorts. Results: In addition to highly significant associations with APOE across all samples, several non-APOE variants showed nominal evidence for association in individual cohorts. However, the observed genetic effects were quite variable, and overall showed little consistency. Currently, genotyping is completed for 20 of the 27 loci and upon combining results from all four samples, the most significant associations were observed for TF (P 0.007), CHRNB2 (P 0.02), ACE (P 0.07), and PSEN1 (P 0.1). Conclusions: Our findings provide further support that these genes may contain genuine AD risk-alleles of modest effect.