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Plasma homocysteine concentration is a risk factor for schizophrenia

 
  September, 23 2005 20:40
your information resource in human molecular genetics
 
     
It is known that both genetic and environmental factors contribute to the aetiology of schizophrenia, but the precise underlying causes of the disorder are yet to be fully elucidated. It has been proposed that elevated plasma homocysteine concentration is a risk factor for schizophrenia, but the results of previous epidemiological studies have been inconsistent. Homocysteine is a sulphur containing amino-acid derived from the demethylation of the essential amino-acid methionine, a process catalyzed by the enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR). A common functional polymorphism exists in MTHFR gene, localized on chromosome 1p36.3, which alters the activity of the expressed enzyme. It has been previously demonstrated that individuals homozygous for the T allele of this polymorphism have about 25% higher homocysteine levels than those with the normal homozygous C genotype.

In an article to be published in the journal Molecular Psychiatry, Dr Muntjewerff and colleagues at the Nijmegen Mental Health Institute in The Netherlands, report the findings of a meta-analysis of eight retrospective studies (comprising of 812 cases and 2113 control subjects) to examine the association between homocysteine and schizophrenia. They conclude that higher homocysteine levels are associated with a 70% higher risk of schizophrenia. In addition, the authors also performed a meta-analysis of ten studies (comprising of 2265 cases and 2721 control subjects) on the homozygous (TT) genotype of the MTHFR 677C>T polymorphism. Interestingly, they found that the TT genotype was associated with a 36% higher risk of schizophrenia compared to the CC genotype.

The authors conclude that the elevated risk of schizophrenia associated with the homozygous genotype of the MTHFR 677C>T polymorphism provides support for causality between disturbed homocysteine metabolism and risk of schizophrenia.

Link to article in Molecular Psychiatry



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