Candidate gene analysis of semaphorins in patients with Alzheimer's disease.
Semaphorins of the SemaIV family are expressed in neurons and decreased in brains from patients with Alzheimer's disease (AD). Accumulation of an internalized form of Sema3A is associated with degeneration of neurons, making these molecules candidates for the development of AD. Single nucleotide polymorphisms (SNPs) rs36026860 and rs28469467 in Sema3A as well as rs13284404 and rs11526468 in Sema4D were analyzed in a population of 240 patients with AD compared with 222 age-matched controls. None of SNPs in Sema3A were present, either in patients or controls. The distribution of the Sema4D rs11526468 and rs13284404 SNPs was not significantly different between patients and controls, even stratifying for gender or age at onset. In silico analysis predicted that rs11526468 and rs28469467 are probably damaging. This high degree of conservation of Sema3A suggests a very important role for this protein. However, neither Sema3A nor Sema4D likely influence the susceptibility to AD.
Villa
Chiara
C
Department of Neurological Sciences, Dino Ferrari Center, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Milan, Italy.
Venturelli
Eliana
E
Fenoglio
Chiara
C
De Riz
Milena
M
Scalabrini
Diego
D
Cortini
Francesca
F
Serpente
Maria
M
Cantoni
Claudia
C
Bresolin
Nereo
N
Scarpini
Elio
E
Galimberti
Daniela
D
D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D015703:Antigens, CD / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040121:Semaphorin-3A / Q000235:genetics*; D039961:Semaphorins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012737:Sex Factors; D013997:Time Factors
D015703:Antigens, CD; D053327:Apolipoprotein E4; C093224:CD100 antigen; C108639:SEMA3A protein, human; D040121:Semaphorin-3A; D039961:Semaphorins