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Genetic Association of Neurotrophic Tyrosine Kinase Receptor Type 2 ( NTRK2 ) With Alzheimer's Disease
Author(s) -
Chen Zuomin,
Simmons Micah S.,
Perry Rodney T.,
Wiener Howard W.,
Harrell Lindy E.,
Go Rodney C.P.
Publication year - 2007
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30607
Subject(s) - tropomyosin receptor kinase b , genetic association , tyrosine kinase , association (psychology) , tropomyosin receptor kinase c , neurotrophic factors , biology , medicine , genetics , receptor , genotype , psychology , platelet derived growth factor receptor , gene , single nucleotide polymorphism , growth factor , psychotherapist
Brain‐derived neurotrophic factor (BDNF)/tyrosine receptor kinase (TRK) signaling pathway activates a wide range of downstream intracellular cascades, regulating neuronal development and plasticity, long‐term potentiation, and apoptosis. The NTRK family encodes the receptors TRKA, TRKB, and TRKC, to which the neurotrophins, nerve growth factor (NGF), BDNF and neurotrophin‐3 (NT‐3) bind, respectively, with high affinity. Signaling through these receptors appears to be compromised in Alzheimer's disease (AD). This study is the most comprehensive investigation of genetic variants of NTRK2 , and the first to show significant association between NTRK2 with AD. Fourteen single nucleotide polymorphisms (SNPs), located in 8 of 18 linkage disequilibrium (LD) blocks, were genotyped in 203 families with at least two AD affected siblings with mean age of onset (MAO) of 70.9 ± 7.4 years and one unaffected sibling from the NIMH‐ADGJ dataset. Family based association testing found no single SNP association, however, significant associations were found for two and three locus haplotypes (P = 0.012, P = 0.009, respectively) containing SNPs rsl624327, rsl443445, and rs378645. These SNPs are located in areas of the gene containing sequences that could be involved in alternative splicing and/or regulation of NTRK2 . Our results suggest that NTRK2 may be a genetic susceptibility gene contributing to AD pathology. © 2007 Wiley‐Liss, Inc.