The association of MYD88 polymorphism with schizophrenia in the Tunisian population

Abstract

Since abnormal inflammation triggered by Toll-like receptors was well described in schizophrenia pathophysiology, the altered activation of MyD88, the adaptor protein of the majority of these receptors, has gained attention. However, the genetic predisposition through MYD88 variants to schizophrenia is still unexplored. Therefore, we investigated the possible association between rs4988457 and schizophrenia in the Tunisian population. We performed a case-control study including 145 schizophrenic patients and 157 controls. All participants were genotyped for rs4988457 by PCR-RFLP. The genotypic and allelic frequencies were compared between patients and controls based on clinical characteristics. The statistical analysis of our results revealed a significant decrease of GG+CG genotypes and G allele frequencies in patients with the undifferentiated type of schizophrenia compared to controls (p-value=0.03; OR=0.4, p-value=0.02; OR=0.4, respectively) according to the dominant model. Further analyses showed that SANS and SAPS scores, before treatment, were significantly lower in patients carrying CC+CG compared to patients with CC (p-value=0.00007, p-value=0.003, respectively). After treatment, psychiatric scales scores decreased significantly in CC carriers (SANS: p-value=0.0001, SAPS: p-value=0.000002, BPRS: p-value=0.000001); meanwhile, these scores did not differ in CC+CG carriers (p-value=0.9, p-value=0.3, p-value=0.8, respectively). In addition, BPRS scores were significantly higher in CC+CG carriers compared to CC carriers (p-value=0.01) after treatment. In conclusion, the current study suggests that MYD88 rs4988457 could be associated with protection from the undifferentiated type and positive and negative symptoms of schizophrenia in the Tunisian population. Additionally, rs4988457 could be a pharmacogenetic marker of decreased efficiency of antipsychotic treatment against brief symptoms of schizophrenia.