No Evidence for Association between Tyrosine Hydroxylase Gene Val81Met Polymorphism and Susceptibility to Tardive Dyskinesia in Schizophrenia

Abstract

ObjectiveTyrosine hydroxylase (TH) is the rate-limiting enzyme in dopamine biosynthesis. Because the TH Val81Met polymorphism is located in the amino-terminal regulatory domain of the tetrameric enzyme, it is a candidate marker for susceptibility to dopamine-related traits. We investigated the hypothesis that TH Val81Met polymorphism can influence susceptibility to tardive dyskinesia (TD) in schizophrenia.MethodsTH Val81Met polymorphism was analyzed by PCR-based methods in 83 schizophrenic patients with TD and 126 schizophrenic patients without TD, matched for antipsychotic drug exposure and other relevant variables.ResultsThere was no significant association of the genotype and allele frequencies determined by the TH Val81Met polymorphism between TD and non-TD patients. In addition, there was no significant difference in terms of total Abnormal Involuntary Movement Scale scores among the three genotype groups.ConclusionWithin the limitations imposed by the size of the clinical sample, these findings suggest that the Val81Met polymorphism of the TH gene does not contribute significantly to the risk for TD.

Association between Antipsychotics-Induced Restless Legs Syndrome and Tyrosine Hydroxylase Gene Polymorphism

“…NIaIII cleaves the Met81 allele into three fragments of 173, 140, 91bp, and the Val81 allele into two fragments of 313 and 91bp. 26 …”

Putative Role of Pharmacogenetics to Elucidate the Mechanism of Tardive Dyskinesia in Schizophrenia

“…The rate-limiting step in the synthesis of dopamine is the hydroxylation of the amino acid tyrosine to levodopa via tyrosine hydroxylase (TH) [125]. The supposedly functional TH Val81Met polymorphism showed no association at all with TD in Korean patients with schizophrenia [126]. Although an association between certain variants of the dopamine catalyzing enzyme COMT gene has been described [115,127,128], meta-analysis have shown that the most important functional COMT Val158Met (rs4680) variant shows very little association with TD [115,128,129].…”

Analysis of genetic variations in the human melatonin receptor (MTNR1A, MTNR1B) genes and antipsychotics-induced tardive dyskinesia in schizophrenia

“…Therefore, there are very likely factors other than dopamine receptors contributing to the pathogenesis of antipsychoticsinduced TD, and many studies have investigated candidate genes with presumed associations with incidence of TD. In Asian populations, for example, Val81Met polymorphisms in the gene of tyrosine hydroxylase, a rate-limiting enzyme in dopamine biosynthesis, have been found not to be associated with TD (Lee et al 2009), and Ala9Val polymorphism in the gene of manganese superoxide dismutase, which can reduce oxidative stress, might be related to the severity of TD (Kang et al 2008). However, we suggest that the melatonin receptors OR, odds ratio.…”