A specific genetic factor may play a role in predicting the occurrence of tardive dyskinesia (TD), according to new findings.
A multinational group of researchers conducted a meta-analysis of 2 data sets to determine the relationship between a particular gene and a slow dyskinesia event. They also added their own new data to the analysis.
The first data set consisted of 217 patients from the United States. and Canada who were diagnosed with schizophrenia. The second set of patients included 20 patients with schizophrenia and 41 patients with schizophrenia without initial TD.
A previous study has shown that the HSPG2 gene or the Perlecan gene is significantly associated with tardive dyskinesia in Japanese schizophrenic patients and a subsequent independent study was able to confirm the findings. Another study examining the lack of the HSPG2 gene in European and Israeli patients with schizophrenia showed that, as in mouse models, involuntary chewing movements were reduced.
Perlecan gene mutations occurred in patients with chondrodystrotic myotonia, or Schwartz-Jampel syndrome, as well as in relation to skeletal muscle aging. Perlecan is also part of the mixture that creates the blood-brain barrier and is likely to be able to play a neuroprotective role after ischemic stroke, the researchers write. The more the Perlecan gene researchers understand, the better the understanding of the role the protein plays in TD, the researchers said.
The researchers received allele measurements for patients with tardive dyskinesia and controls for their research, including the two sets of data. The studies included patients with various backgrounds, such as: Japanese, Hebrew, European and African.
The authors of the study reported that their initial data did not show significant TD or severity as measured by AIMS scores. In other samples from the meta-analysis, the gene was not associated with AIMS transformed scores or slow dyskinesia event.
Of a total of 324 patients with TD and 515 negative TD, the researchers found that the G allele was significantly associated with tardive dyskinesia. There seems to be no significant heterogeneity between the studies, including their post-analysis, they said.
After filtering the results of the study by age, the researchers learned that they seem to affect the findings. Filtering for sex also seems to affect the trend, they wrote.
All this led the researchers to believe that the risk of late dyskinesia "reflects many genetic factors," they wrote. The use of long-term studies involving the examination of fluctuations in late dyskinesia could support this idea another day.
"International efforts are necessary to provide additional independent reproductions in large specimens, especially for small-scale genetic associations," the researchers concluded. "In addition, secondary allele frequencies differed among ethnicities, and findings may also be more relevant to the East Asian samples in which the original findings were found."
Replication studies in patients in different ethnicities could provide information as to whether the genetic correlation is particularly pronounced in Eastern Asians.
The study, "Investigation of the HSPG2 gene in late dyskinesia – new data and meta-analysis", was published in the journal Frontiers in Pharmacology.