Sunday , April 18 2021

Genes can predict the occurrence of tardive dyskinesia



tardive dyskinesia

A specific genetic factor may play a role in predicting the occurrence of tardive dyskinesia (TD), according to new findings.

A multinational team of researchers conducted a meta-analysis of two sets of data to determine the relationship between a specific gene and the occurrence of tardive dyskinesia. They also added their own new data to the analysis.

The first set of data included 217 US and Canadian patients who were diagnosed with schizophrenia. The second group of patients included 20 patients with schizophrenia and 41 schizophrenic patients without DT at baseline.

An earlier study demonstrated that the HSPG2 gene, or Perlecan gene, was significantly associated with tardive dyskinesia in Japanese schizophrenic patients and a subsequent independent study was able to confirm the findings. Another study examining a deficiency of the HSPG2 gene in European and Israeli patients with schizophrenia showed that, as in mouse models, inadvertent chewing movements were reduced.

Mutations in the Perlecan gene have appeared in patients with chondrodistrophic myotonia, or Schwartz-Jampel syndrome, as well as linked to skeletal muscle aging. Perlecan is also part of the mix that creates the blood-brain barrier, and it may even play a neuroprotective role after the ischemic stroke, the researchers wrote. The more researchers understand the Perlecan gene, the better the understanding of the role that protein plays in DT, the researchers note.

The researchers obtained allele counts for patients with tardive dyskinesia and controls for their investigation, including both sets of data. The studies included patients from various backgrounds, including: Japanese, Jewish, European, and African American.

The study authors said that their original data did not show any significant occurrence or severity of TD as measured by scores (AIMS). In the other samples from the meta-analysis, the gene was not associated with transformed AIMS scores or the occurrence of tardive dyskinesia.

Of a total of 324 patients with DT and 515 controls negative for DT, the researchers found that the G allele was significantly linked to tardive dyskinesia. There does not appear to be any significant heterogeneity among the studies, including in their meta-analysis, they said.

After filtering the study results by age, the researchers found that they appeared to affect the results. Filtering by sex also seems to have a tendency effect, they wrote.
All of this has led researchers to believe that the risk of tardive dyskinesia "reflects multiple genetic factors," they wrote. Using long-term studies, which include looking at fluctuations in tardive dyskinesia, one day might support this idea further.

"International efforts are needed to provide additional independent replications in large samples, especially for genetic associations with small effect sizes," the researchers concluded. "In addition, the smaller allelic frequencies differed between the ethnicities, and the findings may also be more relevant for East Asian samples in which the original findings were found."

Replication studies in patients of various ethnicities could provide insight, they noted, to find out if the genetic association is remarkably strong 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.


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