Influence of the Glu298Asp polymorphism of NOS3 on age at onset and homocysteine levels in AD patients.
The distribution of the Glu298Asp polymorphism in NOS3 gene was determined in 405 Italian patients with "probable" Alzheimer's disease (AD) compared with 253 age-matched controls. Total plasma homocysteine (tHcy) levels were evaluated in 97 patients and 23 controls, and were correlated with the Glu298Asp genotype. A significantly increased frequency of the Glu/Glu genotype in late onset AD (LOAD) patients was found. tHcy levels were significantly increased in patients compared with controls and, notably, higher in LOAD than in early onset AD (EOAD). Stratifying by the Glu298Asp genotype, a trend toward an increase of tHcy was present in Glu/Glu homozygous. This wild type genotype seems to be associated with LOAD. tHcy levels are significantly increased in AD compared with controls and, moreover, higher in LOAD than in EOAD, possibly in correlation with the microvascular disease occurring with aging. Besides, a contribution of the Glu/Glu genotype in increasing tHcy levels has been observed.
Guidi
Ilaria
I
Department of Neurological Sciences, Dino Ferrari Center, University of Milan, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milan, Italy.
Galimberti
Daniela
D
Venturelli
Eliana
E
Lovati
Carlo
C
Del Bo
Roberto
R
Fenoglio
Chiara
C
Gatti
Alberto
A
Dominici
Roberto
R
Galbiati
Sara
S
Virgilio
Roberta
R
Pomati
Simone
S
Comi
Giacomo P
GP
Mariani
Claudio
C
Forloni
Gianluigi
G
Bresolin
Nereo
N
Scarpini
Elio
E
D017677:Age Distribution; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism*; D019943:Amino Acid Substitution; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics; D005820:Genetic Testing / Q000379:methods; D005973:Glutamine / Q000235:genetics; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D011110:Polymorphism, Genetic / Q000235:genetics; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D013223:Statistics as Topic
D006710:Homocysteine; D005973:Glutamine; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III