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Updated: Jul 9, 2026

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Neuronal nitric oxide synthase C276T polymorphism increases the risk for frontotemporal lobar degeneration
E Venturelli1, C Villa, E Scarpini
1Department of Neurological Sciences, Dino Ferrari Center, University of Milan, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
Abstract:
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.
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