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No association between polymorphisms of methylenetetrahydrofolate reductase gene and schizophrenia in both Chinese and Scottish populations

Molecular Psychiatry volume 9, pages 1063–1065 (2004)Cite this article

SIR—Methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a methyl donor for the remethylation of homocysteine to methionine. Patients with severe MTHFR deficiency have a range of vascular and schizophrenia-like disturbances with a variable age at onset. A common mutation C677T in the MTHFR gene is responsible for the reduced enzyme activity of MTHFR.1 The CT/TT genotype is associated with increased risk of neural tube defects in association with first trimester prenatal malnutrition.2 Evidence from Dutch hunger winter has indicated that first trimester prenatal nutritional deficiency is also associated with increased risk of schizophrenia. In light of a possible association of MTHFR with schizophrenia, several studies have examined the common C677T variant as a risk factor for schizophrenia; however, discrepant results have been observed between schizophrenia and the 677 TT genotype. Another common mutation A1298C by itself does not cause hyperhomocysteinemia as compared to the C677T variant.3 However, combined heterozygosity for the A1298C and C677T variant (AC/CT) may be associated with reduced MTHFR specific activity and hyperhomocysteinemia.3 Only one study to date has investigated the A1298C variant in schizophrenia4 and no association was found with this variant in Caucasians. However, they did report an increased frequency of the 677TT.

In the present study, we have examined both C667T and A1298C variants in two large racially distinct populations using two sets of analyses to try to resolve these conflicting results. In the Han Chinese population, DNA samples from 230 unrelated cases with schizophrenia or schizoaffective disorder and 251 controls from Shanghai were examined. A total of 267 schizophrenic probands and their biological parents from Sichuan province were also examined using transmission disequilibrium test (TDT) analysis. At the same time, we have investigated a large set of well-characterized case–control samples from the Scottish population with European ancestry. Subjects were 426 cases and 628 control individuals. Two senior psychiatrists made clinical diagnosis. All Chinese and Scottish cases met the DSM-III-R criteria for schizophrenia or schizoaffective disorder. Written informed consents were obtained from all patients or their relatives and control individuals. The two variants were genotyped by using standard PCR-RFLP analysis. The primers and the procedures were performed as per the methods of Frosst et al1 and ven der Put et al,3 respectively.

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Authors and Affiliations

  1. Department of Mental Health and Medical School, University of Aberdeen, Aberdeen, UK

    L Yu, Z Robertson, J Dean, P Yates, M Sinclair, C Crombie & D St Clair

  2. Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China

    L Yu

  3. Bio-X Life Science Research Center, Shanghai Jiao Tong University, Shanghai, China

    L Yu & L He

  4. Division of Psychological Medicine, Institute of Psychiatry, London, UK

    T Li & D A Collier

  5. West China Hospital, Sichuan University, China

    T Li

  6. Shanghai Institute of Mental Health, Shanghai, China

    N F Gu & G Y Feng

  7. Ravenscraig Hospital, Greenock, Scotland, UK

    N Walker

  8. NHGG, INS, SIBS, Chinese Academy of Sciences, China

    L He

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  1. L Yu
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  2. T Li
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  3. Z Robertson
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  4. J Dean
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  6. G Y Feng
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  7. P Yates
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  8. M Sinclair
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  9. C Crombie
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  10. D A Collier
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  11. N Walker
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  12. L He
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  13. D St Clair
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Correspondence to L He or D St Clair.

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Yu, L., Li, T., Robertson, Z. et al. No association between polymorphisms of methylenetetrahydrofolate reductase gene and schizophrenia in both Chinese and Scottish populations. Mol Psychiatry 9, 1063–1065 (2004). https://doi.org/10.1038/sj.mp.4001566

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