C677T and A1298C gene polymorphisms and sporadic early-onset Alzheimer’s disease


Alzheimer’s disease (AD) is a genetically complex and heterogeneous disorder. Although the clinical manifestations and the pathological features have been well elucidated, a clear etiology of AD is still unknown to this day. In the past few decades, investigations have elucidated that both the genetic and the environmental factors are capable of causing the development of AD. We report a patient with clinically diagnosed earlyonset Alzheimer's disease, age of onset 45 years. Genetic analysis revealed two MTHFR heterozygous polymorphisms C677T and A1298C.

Share and Cite:

Mansouri, L. , Klai, S. , Fekih-Mrissa, N. , Gritli, N. and Mrissa, R. (2013) C677T and A1298C gene polymorphisms and sporadic early-onset Alzheimer’s disease. Advances in Alzheimer's Disease, 2, 132-134. doi: 10.4236/aad.2013.24018.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Liu, H., Yang, M., Li, G.M., et al. (2010) The MTHFR C677T polymorphism contributes to an increased risk for vascular dementia: A meta-analysis. Journal of the Neurological Sciences, 294, 74-80. http://dx.doi.org/10.1016/j.jns.2010.04.001
[2] Sakamoto, S., Ishii, K., Sasaki, M., et al. (2002) Differences in cerebral metabolic impairment between early and late onset types of Alzheimer’s disease. Journal of the Neurological Sciences, 200, 27-32. http://dx.doi.org/10.1016/S0022-510X(02)00114-4
[3] Zekanowski, C., Styczyńska, M., Peplońska, B., et al. (2003) Mutations in presenilin 1, presenilin 2 and amyloid precursor protein genes in patients with early-onset Alzheimer’s disease in Poland. Experimental Neurology, 184, 991-996. http://dx.doi.org/10.1016/S0014-4886(03)00384-4
[4] Canua, E., Frisoni, G.B., Agosta, F., et al. (2012) Early and late onset Alzheimer’s disease patients have distinct patterns of white matter damage. Neurobiology of Aging, 33, 1023-1033. http://dx.doi.org/10.1016/j.neurobiolaging.2010.09.021
[5] Rogaeva, E. (2002) The solved and unsolved mysteries of the genetics of early-onset Alzheimer’s disease. Neuro-Molecular Medicine, 2, 1-10. http://dx.doi.org/10.1385/NMM:2:1:01
[6] Seripa, D., Dal Forno, G., Matera, G., et al. (2003) Methylenetetrahydrofolate reductase and angiotensin converting enzyme gene polymorphisms in two genetically and diagnostically distinct cohort of Alzheimer patients. Neurobiology of Aging, 24, 933-939. http://dx.doi.org/10.1016/S0197-4580(03)00040-X
[7] Miller, S.A., Dykes, D.D. and Polesky, H.S. (1998) Simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Research, 16, 1215. http://dx.doi.org/10.1093/nar/16.3.1215
[8] Mendez, M.F., Lee, A.S., Joshi, A. and Shapira, J.S. (2012) Nonamnestic presentations of early-onset Alzheimer’s disease. American Journal of Alzheimer’s Disease and Other Dementias, 27, 413-420.
[9] Smits, L.L., Pijnenburg, Y.A., Koedam, E.L., van der Vlies, A.E., Reuling, I.E., Koene, T., Teunissen, C.E., Scheltens, P. and van der Flier, W.M. (2012) Early onset Alzheimer’s disease is associated with a distinct neuropsychological profile. Journal of Alzheimer’s Disease, 30, 101-108.
[10] Cho, H., Seo, S.W., Kim, J.-H., et al. (2013) Changes in subcortical structures in early-versus late-onset Alzheimer’s disease. Neurobiology of Aging, 34, 1740-1747.
[11] Antonell, A.L. and Altirriba, J., et al. (2013) A preliminary study of the whole-genome expression profile of sporadic and monogenic early-onset Alzheimer’s disease. Neurobiology of Aging, 34, 1772-1778.
[12] Isotalo, P.A., Wells, G.A. and Donnelly, J.G. (2000) Neonatal and fetal methylenetetrahydrofolate reductase genetic polymorphisms: An examination of C677T and A1298C mutations. The American Journal of Human Genetics, 67, 986-990.
[13] Humphrey, L.L., Fu, R., Rogers, K., Freeman, M. and Helfand, M. (2008) Homocysteine level and coronary heart disease incidence: A systematic review and metaanalysis. Mayo Clinic Proceedings, 83, 1203-1212. http://dx.doi.org/10.4065/83.11.1203
[14] Klerk, M., Verhoef, P., Clarke, R., Blom, H.J., Kok, F.J., Schouten, E.G. and MTHFR Studies Collaboration Group (2002) MTHFR 677C→T polymorphism and risk of coronary heart disease: A meta-analysis. JAMA, 288, 2023- 2031. http://dx.doi.org/10.1001/jama.288.16.2023
[15] Seshadri, S., Beiser, A., Selhub, J., Jacques, P.F., Rosenberg, I.H., D’Agostino, R.B., Wilson, P.W. and Wolf, P.A. (2002) Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. The New England Journal of Medicine, 46, 476-483. http://dx.doi.org/10.1056/NEJMoa011613
[16] Copede, F. (2010) One-carbon metabolism and Alzheimer’s disease: Focus on epigenetics. Current Genomics, 14, 246-260. http://dx.doi.org/10.2174/138920210791233090
[17] Zhanga, M.Y., Miaoa, L., Li, Y.-S., et al. (2012) Meta-analysis of the methylenetetrahydrofolate reductase C677T polymorphism and susceptibility to Alzheimer’s disease. Neuroscience Research, 68, 142-150. http://dx.doi.org/10.1016/j.neures.2010.06.011
[18] Bertram, L. and Tanzi, R.E. (2003) Genetics of Alzheimer’s disease. In: Dickson, D.W., Ed., Neurodegeneration: The Molecular Pathology of Dementia and Movement Disorders, ISN Neuropath Press, Basel, 40-46.
[19] Olson, J.M., Goddard, K.A. and Dudek, D.M. (2002) A second locus for very-late-onset Alzheimer disease: A genome scan reveals linkage to 20p and epistasis between 20p and the amyloid precursor protein region. The American Journal of Human Genetics, 71, 154-161. http://dx.doi.org/10.1086/341034
[20] Bertram, L., Blacker, D., Crystal, A., Mullin, K., Keeney, D., Jones, J., et al. (2000) Candidate genes showing no evidence for association or linkage with Alzheimer’s disease using family-based methodologies. Experimental Gerontology, 35, 1353-1361. http://dx.doi.org/10.1016/S0531-5565(00)00193-5
[21] Bertram, L. and Tanzi, R.E. (2004) The current status of Alzheimer’s disease genetics: What do we tell the patients? Pharmacological Research, 50, 385-396. http://dx.doi.org/10.1016/j.phrs.2003.11.018

Copyright © 2022 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.