Skip to main content
SpringerLink
Log in

Association of Nicotinamide-N-Methyltransferase Gene rs694539 Variant with Epilepsy

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Here, we report the association of the rs694539 variant of nicotinamide-N-methyltransferase gene with epilepsy in a case-control study of 215 patients with epilepsy and 239 healthy controls (χ 2 = 11.641, P = 0.003). The individuals with the GG genotype revealed protection against epilepsy (χ 2 = 5.866, P = 0.015, OR = 0.623, 95 % CI = 0.425–0.915), whereas the individuals with the AA genotype showed statistically significant increased risk for epilepsy (χ 2 = 8.676, P = 0.003, OR = 5.479, 95 % CI = 1.553–19.337). In addition, the G allele was protective against epilepsy (χ 2 = 8.676, P = 0.003, OR = 0.183, 95 % CI = 0.052–0.644); on the contrary, the A allele was a genetic risk factor for epilepsy (χ 2 = 5.866, P = 0.015, OR = 1.604, 95 % CI = 1.093–2.354). Stratification analysis revealed that the association was statistically significant in male patients with epilepsy (χ 2 = 6.682, P = 0.035). However, the statistical power was only 0.33 in female patients with epilepsy (χ 2 = 5.275, P = 0.072). This finding, for the first time, suggests the involvement of the NNMT gene rs694539 variant in the etiology of epilepsy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ngugi AK, Bottomley C, Kleinschmidt I, Sander JW, Newton CR (2010) Estimation of the burden of active and life-time epilepsy: a meta-analytic approach. Epilepsia 51:883–890

    Article  PubMed  PubMed Central  Google Scholar 

  2. Bhalla D, Godet B, Druet-Cabanac M, Preux PM (2011) Etiologies of epilepsy: a comprehensive review. Expert Rev Neurother 11:861–876

    Article  PubMed  Google Scholar 

  3. Pandolfo M (2011) Genetics of epilepsy. Semin Neurol 31:506–518

    Article  PubMed  Google Scholar 

  4. Dean JC, Robertson Z, Reid V, Wang Q, Hailey H, Moore S, Rasalam AD, Turnpenny P et al (2008) A high frequency of the MTHFR 677C>T polymorphism in Scottish women with epilepsy: possible role in pathogenesis. Seizure 17(3):269–75

  5. Scheffer IE, Berkovic SF (2003) The genetics of human epilepsy. Trends Pharmacol Sci 24:428–433

    Article  CAS  PubMed  Google Scholar 

  6. Sazci A, Ergul E, Bayulkem K (2004) Association of the C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene in patients with essential tremor in Turkey. Mov Disord 19(12):1472–1476

    Article  PubMed  Google Scholar 

  7. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJ, den Heijer M et al (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10(1):111–3

    Article  CAS  PubMed  Google Scholar 

  8. Scher AI, Wu H, Tsao JW, Blom HJ, Feit P, Nevin RL, Schwab KA (2011) MTHFR C677T genotype as a risk factor for epilepsy including post-traumatic epilepsy in a representative military cohort. J Neurotrauma 28(9):1739–45

    Article  PubMed  Google Scholar 

  9. Ono H, Sakamoto A, Mizoguchi N, Sakura N (2000) Methylenetetrahydrofolate reductase 677C>T mutation and epilepsy. J Inherit Metab Dis 23:525–526

    Article  CAS  PubMed  Google Scholar 

  10. Wu YL, Yang HY, Ding XX, Zhao X, Chen J, Bi P, Sun YH (2014) Association between methylenetetrahydrofolate reductase C677T polymorphism and epilepsy susceptibility: a meta-analysis. Seizure 6:411–416

    Article  Google Scholar 

  11. Aksoy S, Szumlanski CL, Weinshilboum RM (1994) Human liver nicotinamide N-methyltransferase. cDNA cloning, expression, and biochemical characterization. J Biol Chem 269:14835–14840

    CAS  PubMed  Google Scholar 

  12. Sano A, Endo N, Takitani S (1992) Fluorometric assay of rat tissue N-methyltransferases with nicotinamide and four isomeric methylnicotinamides. Chem Pharm Bull (Tokyo) 40(1):153–6

    Article  CAS  Google Scholar 

  13. Souto JC, Blanco-Vaca F, Soria JM, Buil A, Almasy L, Ordoñez-Llanos J, Martín-Campos JM, Lathrop M et al (2005) A genome-wide exploration suggests a new candidate gene at chromosome 11q23 as the major determinant of plasma homocysteine levels: results from the GAIT project. Am J Hum Genet 76(6):925–933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16(3):1215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sazci A, Ozel MD, Ergul E, Aygun C (2013) Association of nicotinamide-N-methyltransferase gene rs694539 variant with patients with nonalcoholic steatohepatitis. Genet Test Mol Biomarkers 17(11):849–853

    Article  CAS  PubMed  Google Scholar 

  16. Sazci A, Ozel MD, Ergul E, Onder ME (2013) Association of nicotinamide-N-methyltransferase (NNMT) gene rs694539 variant with bipolar disorder. Gene 532(2):272–275

  17. Dittmann S, Hennig-Fast K, Gerber S, Seemüller F, Riedel M, Emanuel Severus W, Langosch J, Engel RR et al (2008) Cognitive functioning in euthymic bipolar I and bipolar II patients. Bipolar Disord 10(8):877–887

    Article  PubMed  Google Scholar 

  18. Osher Y, Sela BA, Levine J, Belmaker RH (2004) Elevated homocysteine levels in euthymic bipolar disorder patients showing functional deterioration. Bipolar Disord 6(1):82–86

    Article  CAS  PubMed  Google Scholar 

  19. Carr DF, Whiteley G, Alfirevic A, Pirmohamed M, FolATED study team (2009) Investigation of inter-individual variability of the one-carbon folate pathway: a bioinformatic and genetic review. Pharmacogenomics J 9(5):291–305

    Article  CAS  PubMed  Google Scholar 

  20. Kara I, Sazci A, Ergul E, Kaya G, Kilic G (2003) Association of the C677T and A1298C polymorphisms in the 5,10 methylenetetrahydrofolate reductase gene in patients with migraine risk. Mol Brain Res 111(1–2):84–90

    Article  CAS  PubMed  Google Scholar 

  21. Sazci A, Ergül E, Güzelhan Y, Kaya G, Kara I (2003) Methylenetetrahydrofolate reductase gene polymorphisms in patients with schizophrenia. Mol Brain Res 117(1):104–107

    Article  CAS  PubMed  Google Scholar 

  22. Sazci A, Ergul E, Kucukali I, Kara I, Kaya G (2005) Association of the C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene with schizophrenia: association is significant in men but not in women. Prog Neuropsychopharmacol Biol Psychiatry 29(7):1113–1123

    Article  CAS  PubMed  Google Scholar 

  23. Bromberg A, Lerer E, Udawela M, Scarr E, Dean B, Belmaker RH, Ebstein R, Agam G (2012) Nicotinamide-N-methyltransferase (NNMT) in schizophrenia: genetic association and decreased frontal cortex mRNA levels. Int J Neuropsychopharmacol 15(6):727–737

  24. Wang GX, Zhang Y, Lv ZW, Sun M, Wu D, Chen XY, Wu YM (2014) Female specific association between NNMT gene and schizophrenia in a Hun Chinese population. Int J Med Sci 11(12):1234–1239

Download references

Conflict of Interest

The authors declare no financial or other conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Medical Biology and Genetics, Faculty of Medicine, University of Kocaeli, 41380, Kocaeli, Turkey

    Gensay Sazci, Bilgen Sazci & Ali Sazci

  2. Department of Neurology, Istanbul Faculty of Medicine, University of Istanbul, 34260, Capa, Istanbul, Turkey

    Halil Atilla Idrisoglu

Authors
  1. Gensay Sazci
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bilgen Sazci
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ali Sazci
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Halil Atilla Idrisoglu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ali Sazci.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sazci, G., Sazci, B., Sazci, A. et al. Association of Nicotinamide-N-Methyltransferase Gene rs694539 Variant with Epilepsy. Mol Neurobiol 53, 4197–4200 (2016). https://doi.org/10.1007/s12035-015-9364-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-015-9364-2

Keywords

Search

Navigation