A specific genetic factor may play a role in the presence of late dyskinesia (TD), according to new findings.
A multinational team of researchers carried out a meta-analysis of two sets of data to determine the relationship between a particular gene and the occurrence of late diagnosis. They added their own new data to the analysis.
The first set of data included 217 patients in the US and Canada who were diagnosed with schizophrenia. The second set of patients included 20 patients with schizophrenia and 41 patients with schizophrenia without TD at baseline.
A previous study demonstrated that the HSPG2 gene or the Perlecan gene was significantly associated with late dyskinesia in Japanese schizophrenic patients and an independent study afterwards was able to confirm the results. Another study examining a deficiency of the HSPG2 gene in European and Israeli patients with schizophrenia showed that, as with mice, inadequate chewing movements were reduced.
Mutations of the perlecan gene have occurred in patients with chondrodystrophic myotonia or Schwartz-Jampel syndrome, as well as aging of skeletal muscles. Perlecan is also a part of the mixture that creates the blood-brain barrier and it is possible that it may play a neuroprotective role as a result of ischemic stroke, the researchers wrote. Researchers have more understanding of the Perlecan gene, better understanding the role played by proteins in TD, the investigators noted.
The researchers obtained a number of alleles for patients with late dyskinesia and controls for their investigation, including both sets of data. The studies included patients from several environments, including: Japanese, Jews, Europeans and African Americans.
The authors of the study said their original data showed no significant TD or severity as measured by scores (AIMS). In the other meta-analysis samples, the gene was not associated with transformed AIMS scores or late-onset dyskinesia.
From a total of 324 TD patients and 515 negative TD controls, the investigators found that G allele was significantly related to late dyskinesia. There does not seem to be significant heterogeneity among studies, including their meta-analysis, they said.
After filtering the results of the study by age, the researchers found that it seems to affect the results. Filtering for sex also seemed to have an effect on the trend, they wrote.
All this has led researchers to believe that the risk of late dyskinesia "reflects more genetic factors," they wrote. Using long-term studies, including the examination of late dyskinetic fluctuations, could support this idea once again.
International efforts are needed to provide additional independent replications in large samples, especially for small-effect genetic associations, investigators concluded. In addition, frequencies of minor alleles differ across ethnic populations, and findings may also be more relevant to evidence in East Asia, where the findings were found. "
Replication studies on patients from different ethnic groups could provide a perspective, as they have noticed, if the genetic association is particularly strong in East Asia.
The study, "Investigating the HSPG2 gene in late dyskinesia – new data and meta-analysis," was published in the journal Borders in pharmacology.