Neuronal nitric oxide synthase C276T polymorphism increases the risk for frontotemporal lobar degeneration.
The neuronal nitric oxide synthase (nNOS) is abundantly expressed in the brain and its transcripts have been found in the frontal cerebral cortex. Eighty-nine patients with different neurodegenerative tau-related disorders, including 71 patients with frontotemporal lobar degeneration (FTLD), 12 with progressive supranuclear palsy (PSP) and 6 with corticobasal degeneration (CBD), were genotyped for the C276T single nucleotide polymorphism (SNP) in exon 29 of the nNOS gene and compared with 190 age-matched controls (CON). A significantly increased allelic frequency of the T allele was observed in patients compared with CON (40.4% vs. 29.7%, P = 0.014, OR: 1.94, CI: 1.15-3.27). Considering each disorder separately, significance was reached for FTLD only (39.4%, P = 0.0248 versus controls, OR: 1.96, CI: 1.11-3.47). However, the frequency of the T allele was elevated also in patients with PSP (45.8%) and CBD (41.7%). No differences were observed stratifying according to gender or apolipoprotein E status. The C276T SNP acts as risk factor for sporadic FTLD, possibly influencing NOS1 transcription. Studies in larger populations are needed to confirm its role in PSP and CBD.
Venturelli
E
E
Department of Neurological Sciences, Dino Ferrari Center, University of Milan, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
Villa
C
C
Scarpini
E
E
Fenoglio
C
C
Guidi
I
I
Lovati
C
C
Marcone
A
A
Cortini
F
F
Scalabrini
D
D
Clerici
F
F
Bresolin
N
N
Mariani
C
C
Cappa
S
S
Galimberti
D
D
D000368:Aged; D001921:Brain / Q000201:enzymology* / Q000503:physiopathology; D004252:DNA Mutational Analysis; D003704:Dementia / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000201:enzymology; D052248:Nitric Oxide Synthase Type I / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors
D005819:Genetic Markers; D052248:Nitric Oxide Synthase Type I