NeuroMolecular Medicine

, 13:167

The 894G > T (Glu298Asp) Variant in the Endothelial NOS Gene and MTHFR Polymorphisms Influence Homocysteine Levels in Patients with Cognitive Decline

  • Nadia Ferlazzo
  • Gaetano Gorgone
  • Daniela Caccamo
  • Monica Currò
  • Salvatore Condello
  • Francesco Pisani
  • Fabrizio Vernieri
  • Paolo Maria Rossini
  • Riccardo Ientile
Original Paper


The presence and severity of cerebrovascular pathological findings have been shown to increase the risk and stage of cognitive decline observed in Alzheimer’s disease and vascular dementia. Thus, the modification of vascular risk factors seems useful to reduce the risk of dementia regardless of type. Hyperhomocysteinemia has long been known as a major independent risk factor for vascular dysfunction. In this study, we evaluated the relationships between plasma homocysteine levels and genetic risk factors for hyperhomocysteinemia, i.e., the presence of gene variants for methylenetetrahydrofolate reductase (MTHFR) and endothelial nitric oxide synthase (eNOS) in patients with cognitive impairment. Genotyping for MTHFR C677T and eNOS 894G > T polymorphisms was carried out in 69 patients with probable diagnosis of AD and anamnestic mild cognitive impairment, matched for age and gender with 69 healthy volunteers. Patients with MTHFR TT677 genotype showed higher plasma Hcy levels than controls, even after adjustment for folate levels (P < 0.05). Moreover, Hcy plasma levels were higher in cases than controls for any given eNOS genotype. In particular, the presence of eNOS TT894 genotype in patients with cognitive decline resulted significantly associated with increased plasma Hcy levels when compared with controls having the same genotype or patients having other eNOS genotypes (P = 0.02). These data suggest that both MTHFR C677T and eNOS G894T variants should be regarded as genetic risk factors for hyperhomocysteinemia in patients with cognitive decline.


Alzheimer’s disease Cognitive decline Vascular dementia Hyperhomocysteinemia MTHFR eNOS SNPs 


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Nadia Ferlazzo
    • 1
  • Gaetano Gorgone
    • 2
  • Daniela Caccamo
    • 1
  • Monica Currò
    • 1
  • Salvatore Condello
    • 1
  • Francesco Pisani
    • 3
  • Fabrizio Vernieri
    • 4
  • Paolo Maria Rossini
    • 4
  • Riccardo Ientile
    • 1
  1. 1.Department of Biochemical, Physiological and Nutritional SciencesUniversity of MessinaMessinaItaly
  2. 2.Department of Clinical and Experimental Medicine, Medical SchoolUiniversity of CatanzaroCatanzaroItaly
  3. 3.Department of NeurosciencesUniversity of MessinaMessinaItaly
  4. 4.Clinical Neurology (P.M.R.)University Campus Bio-MedicoRomeItaly

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