Association between Val108/158met polymorphism of theCOMTgene and schizophrenia

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Abstract
Schizophrenia is a complex disorder with a multifactorial polygenic inheritance with several genes conferring susceptibility at many genetic locations, each with a small effect. An attractive candidate gene for schizophrenia is the catechol‐O‐methyltransferase (COMT) gene, which is a modulator of dorsolateral prefrontal cortical function. A missense G to A mutation in this gene that results in a substitution of Methionine (Met) for Valine (Val) at codon 108/158 (Val108/158Met) has recently been identified in association to schizophrenia. We compared allele frequencies of the variant Val allele between 96 schizophrenia cases and 80 normal controls. We selected controls from a similar pool to cases in ethnicity and gender. The frequency of the Val allele was significantly higher in schizophrenia cases compared to controls (0.620 vs. 0.506;P = 0.043). Calculation of the population attributable risk suggests that the Val allele accounts for as much as 23% of schizophrenia in this population (range: 3–38%). These results provide support for a role of this variant in the etiopathophysiology of schizophrenia.