title: Lymphocyte-specific protein tyrosine kinase is a novel risk gene for Alzheimer disease.
abstract: Lymphocyte-specific protein tyrosine kinase (LCK) is a lymphoid-specific, Src family protein tyrosine kinase that is known to play a pivotal role in T-cell activation and interact with the T-cell coreceptors, CD4 and CD8. It has been shown to be significantly down-regulated in Alzheimer disease (AD) hippocampus compared with non-demented controls. Furthermore, it is located in a previously identified genetic linkage region (1p34-36) associated with AD. Therefore, we consider it to be a candidate gene for AD. We examined the relationship between AD and the LCK and apolipoprotein E (APOE) genes in 376 AD (including 323 late-onset AD (LOAD) cases and 53 early-onset AD (EOAD) cases) and 378 non-demented controls using a single nucleotide polymorphism (SNP). The polymorphism in intron 1 (+6424 A/G) was significantly associated with AD risk. The odds ratio (OR) for total AD associated with the GG genotype was 1.41 (95% CI=1.06-1.87) and that for LOAD was 1.37 (95%CI=1.02-1.85), while that for APOE-epsilon4 was 5.06 (95% CI=3.60-7.12). In the APOE-epsilon4 non-carrier subgroup, the GG genotype also showed significant association (OR=1.66; 95% CI=1.16-2.38). These results indicate that the LCK is a novel risk gene for AD regardless of the APOE genotype.
authors.affiliation: Department of Geriatric Medicine, Ehime University School of Medicine, Ehime, Japan.
authors.forename: Wangtao
authors.initials: W
authors.lastname: Zhong
authors.forename: Hidehisa D
authors.initials: HD
authors.lastname: Yamagata
authors.forename: Keiko
authors.initials: K
authors.lastname: Taguchi
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Akatsu
authors.forename: Kouzin
authors.initials: K
authors.lastname: Kamino
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Kosaka
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takeda
authors.forename: Ikuko
authors.initials: I
authors.lastname: Kondo
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Miki
mesh_terms: D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D011505:Protein-Tyrosine Kinases