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Vol 48(2014) N 6 p. 835-844; DOI 10.1134/S0026893314060168 Full Text

V.A. Stepanov1,2*, A.V. Bocharova1, A.V. Marusin1, N.G. Zhukova3, V.M. Alifirova3, I.A. Zhukova3

Replicative association analysis of genetic markers of cognitive traits with Alzheimer s disease in the Russian population

1Institute of Medical Genetics, Russian Academy of Medical Scienses, Tomsk, 634050 Russia
2Tomsk State Research University, Tomsk, 634050 Russia
3Siberian State Medical University, Tomsk, 634050 Russia

*vadim.stepanov@medgenetics.ru
Received - 2014-06-02; Accepted - 2014-07-08

A replicative association analysis of Alzheimer's disease (AD) was carried out for 15 genetic markers that have been associated with cognitive disorders in genome-wide association studies. In the Russian population, AD was associated with CSMD1 rs2616984 (OR = 1.50, 95% CI 1.07 - 2.09, p-value = 0.018) and, potentially, with NOTCH4 rs313296 (OR = 1.53, 95% CI 0.98 - 2.39, p-value = 0.06) and NRIP1 rs2229741 (OR = 1.35, 95% CI 0.99 - 1.85, p-value = 0.061). Combinations of epistatically interacting genes (CSMD1 and NRIP1; NOTCH4, CSMD1, and NRIP1; and TLR4, CSMD1, and NRIP1) were identified, along with their genotype combinations that showed a significant association with AD and the highest predictive values. Possible molecular mechanisms of the gene involvement in AD pathogenesis are discussed. A bioinformatics analysis of the biological processes, molecular functions, and protein-protein interactions for the AD genes indicated that the genes may play a modulating or modifying role, acting together in various regulatory and signaling pathways involved in AD.

Alzheimer's disease, association study, genetic markers, gene ontology, Russian population



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