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Vol 47(2013) N 6 p. 827-835;
I.I. Nizamutdinov1*, T.V. Andreeva2,3, V.A. Stepanov4, A.V. Marussin4, E.I. Rogaev2,3, A.S.Zasedatelev1,5, T.V.Nasedkina1

Biochip for Determination of Genetic Markers of Sporadic Alzheimer's Disease Risk

1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia
2Mental Health Research Center, Russian Academy of Medical Sciences, Moscow, 117152 Russia
3Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, 119991 Russia
4Institute of Medical Genetics, Tomsk Research Center, Siberian Division, Russian Academy of Medical Sciences, Tomsk, 634050 Russia
5Moscow Institute of Physics and Technology, Dolgoprudnyi, 141700 Russia

*ignizamutdinov@gmail.com
Received - 2013-06-03; Accepted - 2013-06-26

A biological microchip (biochip) has been developed to study the genetic predisposition to sporadic form of Alzheimer's disease (AD). The biochip allows of genotyping of ten genetic polymorphisms within APOE, TOMM40, APOJ, EXOC3L2, GAB2, A2M, CR1, BIN1, and PICALM genes. The assay includes the amplification of the loci of interest and subsequent allele-specific hybridization of the fluorescently labeled amplicons with oligonucleotides immobilized on the biochip. The genotyping of 166 patients and 128 controls revealed a significant association of APOE allele ε4 with susceptibility to AD (OR = 2.275, 95% CI 1.045- 4.954, p = 0.034). Protective effects were observed for APOE allele ε2 and CLU (rs11136000) allele T (OR = 0.215, 59% CI 0.090-0.516, p = 0.001 and OR = 0.679, 95% CI 0.47-0.99, p = 0.042, respectively). A gene-gene interaction analysis revealed two AD-associated genotype combinations, APOE ε3/ε4 GAB2 G/G (OR = 2.49, 95% CI 1.43-4.32, p = 0.001) and APOE ε4/ε4 GAB2 G/G (OR = 3.55, 95% CI 1.23-10.24, p = 0.015). Based on the results of the combined multivariate analysis, an algorithm was developed to identify the individuals having a higher risk of AD.

Alzheimer's disease, genetic predisposition, genetic polymorphism, genotyping, biochips



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