Nicotinamide-N-methyltransferase (NNMT) in schizophrenia: Genetic association and decreased frontal cortex mRNA levels

International Journal of Neuropsychopharmacology

Volumn 15, Issue 6, 2012, Pages 727-737

  Bromberg, Anna ^a   Lerer, Elad ^b   Udawela, Madhara ^c   Scarr, Elizabeth ^c   Dean, Brian ^c   Belmaker, R H ^a   Ebstein, Richard ^b   Agam, Galila ^a  

^a BEN GURION UNIVERSITY OF THE NEGEV   (Israel)

^b HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^c FLOREY INSTITUTE OF NEUROSCIENCE AND MENTAL HEALTH   (Australia)

Author keywords

Frontal cortex; genetic association; mRNA levels; nicotinamide N methyltransferase (NNMT); schizophrenia

Indexed keywords

BETA ACTIN; CHLORPROMAZINE; GENOMIC DNA; HALOPERIDOL; HOMOCYSTEINE; MESSENGER RNA; NICOTINAMIDE METHYLTRANSFERASE; RISPERIDONE; TRIFLUOPERAZINE;

ADULT; AGED; ARTICLE; AUTOPSY; CARBON METABOLISM; CONTROLLED STUDY; ETHNICITY; FEMALE; FRONTAL CORTEX; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC LINKAGE; GENOTYPE; HAPLOTYPE; HOUSEKEEPING GENE; HUMAN; HYPERHOMOCYSTEINEMIA; INTRON; MALE; MUTATIONAL ANALYSIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; QUANTITATIVE ANALYSIS; REAL TIME POLYMERASE CHAIN REACTION; SCHIZOPHRENIA; SINGLE NUCLEOTIDE POLYMORPHISM;

ADULT; FEMALE; FRONTAL LOBE; GENETIC ASSOCIATION STUDIES; GENOTYPE; HUMANS; LINKAGE DISEQUILIBRIUM; MALE; MIDDLE AGED; NICOTINAMIDE N-METHYLTRANSFERASE; POLYMORPHISM, SINGLE NUCLEOTIDE; RNA, MESSENGER; SCHIZOPHRENIA; YOUNG ADULT;

EID: 84862153143     PISSN: 14611457     EISSN: 14695111     Source Type: Journal    
DOI: 10.1017/S1461145711001179     Document Type: Article

References (48)

1. Akanji AO, Ohaeri JU, Al-Shammri SA, Fatania HR (2007). Associations of blood homocysteine concentrations in Arab schizophrenic patients. Clinical Biochemistry 40, 1026-1031. (Pubitemid 47301802)
2. Aksoy S, Szumlanski CL, Weinshilboum RM (1994). Human liver nicotinamide N-methyltransferase. cDNA cloning, expression, and biochemical characterization. Journal of Biological Chemistry 269, 14835-14840.
3. APA (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Washington, DC: American Psychiatric Association.
4. Applebaum J, Shimon H, Sela BA, Belmaker RH, et al. (2004). Homocysteine levels in newly admitted schizophrenic patients. Journal of Psychiatry Research 38, 413-416. (Pubitemid 38760009)
5. Ben-Shachar D (2002). Mitochondrial dysfunction in schizophrenia : a possible linkage to dopamine. Journal of Neurochemistry 83, 1241-1251. (Pubitemid 35477464)
6. Ben-Shachar D, Karry R (2008). Neuroanatomical pattern of mitochondrial complex I pathology varies between schizophrenia, bipolar disorder and major depression. PLoS One 3, e3676.
7. Bisschops RH, van der Graaf Y, Mali WP, van der Grond J (2004). Elevated levels of plasma homocysteine are associated with neurotoxicity. Atherosclerosis 174, 87-92. (Pubitemid 38595444)
8. Brown AS, Bottiglieri T, Schaefer CA, Quesenberry CP, et al. (2007). Elevated prenatal homocysteine levels as a risk factor for schizophrenia. Archives of General Psychiatry 64, 31-39. (Pubitemid 46041736)
9. Carr DF, Whiteley G, Alfirevic A, Pirmohamed M (2009). Investigation of inter-individual variability of the one-carbon folate pathway: a bioinformatic and genetic review. Pharmacogenomics Journal 9, 291-305.
10. de Jonge R, Tissing WJ, Hooijberg JH, Jansen G, et al. (2009). Polymorphisms in folate-related genes and risk of pediatric acute lymphoblastic leukemia. Blood 113, 2284-2289.
11. Frankenburg FR (2007). The role of one-carbon metabolism in schizophrenia and depression. Harvard Reviews of Psychiatry 15, 146-160. (Pubitemid 47237771)
12. Frosst P, Blom HJ, Milos R, Goyette P, et al. (1995). A candidate genetic risk factor for vascular disease : a common mutation in methylenetetrahydrofolate reductase. Nature Genetics 10, 111-113.
13. Giusti B, Saracini C, Bolli P, Magi A, et al. (2008). Genetic analysis of 56 polymorphisms in 17 genes involved in methionine metabolism in patients with abdominal aortic aneurysm. Journal of Medical Genetics 45, 721-730.
14. Glantz LA, Gilmore JH, Lieberman JA, Jarskog LF (2006). Apoptotic mechanisms and the synaptic pathology of schizophrenia. Schizophrenia Research 81, 47-63. (Pubitemid 41817206)
15. Isobe C, Abe T, Terayama Y (2009). Homocysteine May Contribute to Pathogenesis of RNA Damage in Brains with Alzheimer's Disease. Neurodegenerative Diseases 6, 252-257.
16. Isobe C, Murata T, Sato C, Terayama Y (2005). Increase of total homocysteine concentration in cerebrospinal fluid in patients with Alzheimer's disease and Parkinson's disease. Life Sciences 77, 1836-1843. (Pubitemid 41058987)
17. Joober R, Benkelfat C, Lal S, Bloom D, et al. (2000). Association between the methylenetetrahydrofolate reductase 677C->T missense mutation and schizophrenia. Molecular Psychiatry 5, 323-326. (Pubitemid 30438410)
18. Kale A, Naphade N, Sapkale S, Kamaraju M, et al. (2009). Reduced folic acid, vitamin B(12) and docosahexaenoic acid and increased homocysteine and cortisol in never-medicated schizophrenia patients : implications for altered one-carbon metabolism. Psychiatry Research 175, 47-53.
19. Lau CG, Zukin RS (2007). NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders. Nature Reviews Neuroscience 8, 413-426. (Pubitemid 46789232)
20. Lentz SR (2005). Mechanisms of homocysteine-induced atherothrombosis. Journal of Thrombosis and Haemostasis 3, 1646-1654. (Pubitemid 41716550)
21. Levine J, Agam G, Sela BA, Garver DL, et al. (2005a). CSF homocysteine is not elevated in schizophrenia. Journal of Neural Transmission 112, 297-302. (Pubitemid 40179121)
22. Levine J, Sela BA, Osher Y, Belmaker RH (2005b). High homocysteine serum levels in young male schizophrenia and bipolar patients and in an animal model. Progress in Neuropsychopharmacology and Biological Psychiatry 29, 1181-1191. (Pubitemid 41383518)
23. Levine J, Stahl Z, Sela BA, Gavendo S, et al. (2002). Elevated homocysteine levels in young male patients with schizophrenia. American Journal of Psychiatry 159, 1790-1792.
24. Lipton SA, Kim WK, Choi YB, Kumar S, et al. (1997). Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor. Proceedings of the National Academy of Sciences USA 94, 5923-5928.
25. Malinowska A, Chmurzynska A (2009). Polymorphism of genes encoding homocysteine metabolism-related enzymes and risk for cardiovascular disease. Nutrition Research 29, 685-695.
26. Muntjewerff JW, Kahn RS, Blom HJ, den Heijer M (2006). Homocysteine, methylenetetrahydrofolate reductase and risk of schizophrenia: a meta-analysis. Molecular Psychiatry 11, 143-149. (Pubitemid 43164615)
27. Murray RM (1994). Neurodevelopmental schizophrenia : the rediscovery of dementia praecox. British Journal of Psychiatry 25 (Suppl.), 6-12. (Pubitemid 24331667)
28. Nevo GA, Meged S, Sela BA, Hanoch-Levi A, et al. (2006). Homocysteine levels in adolescent schizophrenia patients. European Neuropsychopharmacology 16, 588-591. (Pubitemid 44781078)
29. Obeid R, Kostopoulos P, Knapp JP, Kasoha M, et al. (2007). Biomarkers of folate and vitamin B12 are related in blood and cerebrospinal fluid. Clinical Chemistry 53, 326-333. (Pubitemid 46338278)
30. Parsons RB, Smith SW, Waring RH, Williams AC, et al. (2003). High expression of nicotinamide N-methyltransferase in patients with idiopathic Parkinson's disease. Neuroscience Letters 342, 13-16. (Pubitemid 36513898)
31. Pfaffl MW (2001). A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Research 29, e45.
32. Postuma RB, Lang AE (2004). Homocysteine and levodopa : should Parkinson disease patients receive preventative therapy? Neurology 63, 886-891. (Pubitemid 39297652)
33. Regland B, Germgard T, Gottfries CG, Grenfeldt B, et al. (1997). Homozygous thermolabile methylenetetrahydrofolate reductase in schizophrenia-like psychosis. Journal of Neural Transmission 104, 931-941. (Pubitemid 27507339)
34. Regland B, Johansson BV, Grenfeldt B, Hjelmgren LT, et al. (1995). Homocysteinemia is a common feature of schizophrenia. Journal of Neural Transmission General Section 100, 165-169.
35. Riederer M, Erwa W, Zimmermann R, Frank S, et al. (2009). Adipose tissue as a source of nicotinamide Nmethyltransferase and homocysteine. Atherosclerosis 204, 412-417.
36. Rodriguez-Oroz MC, Lage PM, Sanchez-Mut J, Lamet I, et al. (2009). Homocysteine and cognitive impairment in Parkinson's disease: a biochemical, neuroimaging, and genetic study. Movement Disorders 24, 1437-1444.
37. Sachdev PS, Valenzuela M, Wang XL, Looi JC, et al. (2002). Relationship between plasma homocysteine levels and brain atrophy in healthy elderly individuals. Neurology 58, 1539-1541. (Pubitemid 34552965)
38. Sano A, Endo N, Takitani S (1992). Fluorometric assay of rat tissue N-methyltransferases with nicotinamide and four isomeric methylnicotinamides. Chemical Pharmacology Bulletin (Tokyo) 40, 153-156.
39. Sazci A, Ergul E, Guzelhan Y, Kaya G, et al. (2003). Methylenetetrahydrofolate reductase gene polymorphisms in patients with schizophrenia. Brain Research. Molecular Brain Research 117, 104-107. (Pubitemid 37123116)
40. Smith ML, Burnett D, Bennett P, Waring RH, et al. (1998). A direct correlation between nicotinamide N-methyltransferase activity and protein levels in human liver cytosol. Biochimica Biophysica Acta 1442, 238-244. (Pubitemid 28530814)
41. Souto JC, Blanco-Vaca F, Soria JM, Buil A, et al. (2005). A genomewide exploration suggests a new candidate gene at chromosome 11q23 as the major determinant of plasma homocysteine levels : results from the GAIT project. American Journal of Human Genetics 76, 925-933. (Pubitemid 40705430)
42. Valentino F, Bivona G, Butera D, Paladino P, et al. (2010). Elevated cerebrospinal fluid and plasma homocysteine levels in ALS. European Journal of Neurology 17, 84-89.
43. Vandesompele J, De Preter K, Pattyn F, Poppe B, et al. (2002). Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biology 3, research0034.
44. Weaver IC, D'Alessio AC, Brown SE, Hellstrom IC, et al. (2007). The transcription factor nerve growth factorinducible protein a mediates epigenetic programming : altering epigenetic marks by immediate-early genes. Journal of Neuroscience 27, 1756-1768. (Pubitemid 46280071)
45. Weinshilboum R (1988). Pharmacogenetics of methylation : relationship to drug metabolism. Clinical Biochemistry 21, 201-210.
46. Yan L, Otterness DM, Weinshilboum RM (1999). Human nicotinamide N-methyltransferase pharmacogenetics : gene sequence analysis and promoter characterization. Pharmacogenetics 9, 307-316. (Pubitemid 29376374)
47. Zhang L, Miyaki K, Araki J, Nakayama T, et al. (2007). The relation between nicotinamide N-methyltransferase gene polymorphism and plasma homocysteine concentration in healthy Japanese men. Thrombosis Research 121, 55-58. (Pubitemid 350025995)
48. Zieminska E, Matyja E, Kozlowska H, Stafiej A, et al. (2006). Excitotoxic neuronal injury in acute homocysteine neurotoxicity: role of calcium and mitochondrial alterations. Neurochemistry International 48, 491-497.