| 1 | J. Psychopharmacol. (Oxford) 2011 Jul 25: 976-81 |
|---|---|
| PMID | 21169389 |
| Title | Hyperhomocysteinemia does not affect global DNA methylation and nicotinamide N-methyltransferase expression in mice. |
| Abstract | DNA methylation is coupled with one-carbon metabolism involving homocysteine/methionine interconversion. Correlation between plasma homocysteine levels and leukocyte global DNA methylation was reported but not always replicated. Nicotinamide N-methyltransferase (NNMT) is a determinant of plasma homocysteine levels. Findings suggest alteration of one-carbon metabolism inschizophreniaetiology; hyperhomocysteinemia was observed inschizophrenia。最近的一项研究由thi的作者s paper found an association betweenNNMTandschizophreniaand decreased post-mortem brainNNMTmRNA levels. The present study assessed the interrelationship between brain and leukocytes global DNA methylation and plasma homocysteine levels, and between hyperhomocysteinemia and brainNNMTexpression. Mice were administered homocysteine in drinking water. Percentage global genome DNA methylation was measured using the cytosine-extension method, andNNMT使用实时作为表达测定ntitative reverse transcriptase PCR (qRT-PCR). Homocysteine administration resulted in a 10-fold increase in plasma homocysteine. However, there was no change in global DNA methylation in lymphocytes or in the frontal cortex. No significant intra-individual correlation was found between global DNA methylation in leukocytes and frontal cortex, suggesting that leukocyte global DNA methylation may not serve as a marker for brain global DNA methylation. No difference was found inNNMTexpression in homocysteine-treated mice compared with control mice. In conclusion, relatively short-term hyperhomocysteinemia in mice does not reproduce or lead to alterations reported in one-carbon metabolism in disorders associated with lifelong elevated plasma homocysteine. |
| SCZ Keywords | schizophrenia |
| 2 | Int. J. Neuropsychopharmacol. 2012 Jul 15: 727-37 |
| PMID | 21791160 |
| Title | Nicotinamide-N-methyltransferase (NNMT) in schizophrenia: genetic association and decreased frontal cortex mRNA levels. |
| Abstract | Emerging evidence suggests impaired one-carbon metabolism inschizophrenia。Homocysteine is one of the key components of one-carbon metabolism. Elevated plasma homocysteine levels were reported inschizophrenia。A linkage study found that nicotinamide-N-methyltransferase (NNMT), an enzyme involved in one-carbon metabolism, is a determinant of plasma homocysteine levels. In an association study the rs694539NNMTsingle nucleotide polymorphism (SNP) was found significantly associated with hyperhomocysteinaemia. Aiming to assess the possible involvement ofNNMTin the aetiology ofschizophreniawe (1) performed an association study of eightNNMTtagged SNPs in 202 families sharing the same ethnic origin including healthy parents and aschizophreniaproband; (2) assessedNNMTmRNA levels in post-mortem frontal cortex ofschizophreniapatients. Genotyping was performed using the ABI SNaPshot and the HRM methods. Individual SNPs and haplotypes were analysed for association using the family-based association test (UNPHASED software).NNMTmRNA levels were measured using RT real-time PCR. In the single SNP analysis, rs694539, previously reported to be associated with hyperhomocysteinaemia, and rs1941404 were significantly associated withschizophrenia(p<0.004 and p=0.033, respectively, following permutation test adjustment). Several haplotypes were also significantly associated withschizophrenia(global p values <0.05 following permutation test adjustment). This is the first study demonstrating an association ofNNMTwithschizophrenia。Post-mortem frontal cortexNNMTmRNA levels were ~35% lower inschizophreniapatients vs. control subjects. Our study favours the notion thatNNMTis involved in the aetiology ofschizophrenia。 |
| SCZ Keywords | schizophrenia |
| 3 | Int J Med Sci 2014 -1 11: 1234-9 |
| PMID | 25317069 |
| Title | Female specific association between NNMT gene and schizophrenia in a Han Chinese population. |
| Abstract | Accumulating evidence has shown that alterations in one carbon metabolism might play an important role in the pathogenesis ofschizophrenia(SZ). Nicotinamide-N-methyltransferase (NNMT) is one of the key enzymes of one-carbon metabolism. To examine whetherNNMTgene was associated with SZ in Han Chinese population, we selected seven single nucleotide polymorphisms (SNPs) inNNMTgene, and investigated its association with SZ from a cohort of 42 SZ patients and 86 healthy controls by Mass-ARRAY technology. Statistical analyses revealed that one (rs694539) of the SNPs in the female subgroup showed significant difference between SZ patients and controls both in genotypic (p= 0.0170) and allelic frequencies (p = 0.0059). We also found that the frequency of haplotype 'A G G C T C T' in the female patients was significantly higher than in controls (p=0.0015). Our results suggest thatNNMTrs694539 may have a role in the etiology of SZ in a Han Chinese female population. |
| SCZ Keywords | schizophrenia |